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Intervirology[JOURNAL]

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Latest Insights on the Diagnostic Approaches and Treatment Strategies of COVID-19.

Hassanein SS, Sharaby MR, Tawfik NM … +5 more , Rashed SA, Adel M, Fayez A, Mansour H, Amer HM

Intervirology · 2022 · PMID 35249006 · Full text

BACKGROUND: COVID-19 has emerged as the most serious pandemic in the 21st century to date. COVID-19 patients may develop various disease symptoms that hinder the accurate clinical diagnosis. SUMMARY: Routine diagnosis of... BACKGROUND: COVID-19 has emerged as the most serious pandemic in the 21st century to date. COVID-19 patients may develop various disease symptoms that hinder the accurate clinical diagnosis. SUMMARY: Routine diagnosis of COVID-19 requires complementary investigations, including computed tomography, immunological assays, and molecular assays like real-time RT-PCR, loop-mediated isothermal amplification, metagenomic next-generation sequencing, and clusters of regularly interspaced short palindromic repeats-based assays. Clinically approved antiviral drugs available for the COVID-19 treatment are very limited. The most common measurements that enhance health condition and patients' viability are conservation fluid management, oxygen therapy, and antibiotics. Several therapeutic options have been developed or repurposed to prevent virus replication and/or modulate the immune response against virus infection. These options include various drugs that affect virus entry and membrane fusion, inhibit polymerase and protease activity, suppress the host pro-inflammatory cytokines, and utilize cell therapy approaches. KEY MESSAGES: In this review, we aimed to provide an up-to-date discussion on the current diagnostic options and therapeutic strategies used to control and manage COVID-19 in clinical and point-of-care settings.

Development of RNA-Based Assay for Rapid Detection of SARS-CoV-2 in Clinical Samples.

Kumar V, Mishra S, Sharma R … +7 more , Agarwal J, Ghoshal U, Khanna T, Sharma LK, Verma SK, Mishra P, Tiwari S

Intervirology · 2022 · PMID 35193136 · Full text

INTRODUCTION: The ongoing spread of pandemic coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of growing concern. Rapid diagnosis and management of SARS-CoV-2 ar... INTRODUCTION: The ongoing spread of pandemic coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of growing concern. Rapid diagnosis and management of SARS-CoV-2 are crucial for controlling the outbreak in the community. Here, we report the development of a first rapid-colorimetric assay capable of detecting SARS-CoV-2 in the human nasopharyngeal RNA sample in less than 30 min. METHOD: We utilized a nanomaterial-based optical sensing platform to detect RNA-dependent RNA polymerase gene of SARS-CoV-2, where the formation of oligo probe-target hybrid led to salt-induced aggregation and change in gold-colloid color from pink to blue visibility range. Accordingly, we found a change in colloid color from pink to blue in assay containing nasopharyngeal RNA sample from the subject with clinically diagnosed COVID-19. The colloid retained pink color when the test includes samples from COVID-19 negative subjects or human papillomavirus-infected women. RESULTS: The results were validated using nasopharyngeal RNA samples from positive COVID-19 subjects (n = 136). Using real-time polymerase chain reaction as gold standard, the assay was found to have 85.29% sensitivity and 94.12% specificity. The optimized method has detection limit as little as 0.5 ng of SARS-CoV-2 RNA. CONCLUSION: We found that the developed assay rapidly detects SARS-CoV-2 RNA in clinical samples in a cost-effective manner and would be useful in pandemic management by facilitating mass screening.

Evaluation of IL-1β and IL-6 Expression following EBNA-1 and BRLF-1 Peptide Treatment in Epstein-Barr Virus-Positive Multiple Sclerosis Patients.

Kianfar R, Ravanshad M, Ghiass MA … +3 more , Rafiee N, Shayeghpour A, Maleki A

Intervirology · 2022 · PMID 35158367 · Full text

INTRODUCTION: Epstein-Barr virus (EBV/HHV-4) has been implicated in the pathogenesis of multiple sclerosis (MS). This study was conducted to investigate the levels of pro-inflammatory cytokines IL-1β and IL-6 in healthy... INTRODUCTION: Epstein-Barr virus (EBV/HHV-4) has been implicated in the pathogenesis of multiple sclerosis (MS). This study was conducted to investigate the levels of pro-inflammatory cytokines IL-1β and IL-6 in healthy EBV carriers and MS patients with prior EBV infection in response to treatment with EBV nuclear antigen 1 (EBNA-1) and replication and transcription activator (BRLF-1/Rta) peptide antigens in whole blood cell culture to assess the cytokine expression across all cells in the peripheral blood. METHODS: Isolated whole blood cells from the included participants were incubated at a concentration of 106 cells/mL with BRLF-1 or EBNA-1. The amount of IL-1β and IL-6 transcripts were measured with quantitative RT-PCR at day 3 after incubation. MTT assay was conducted to examine cytotoxicity of the peptides and their effect on cell viability. Changes in cytokine expression and cell viability were analyzed using one-way and two-way ANOVA, respectively. RESULTS: Ten MS patients and ten healthy donors were enrolled in the study. Treatment with the peptide antigens resulted in increased cytokines expression in both MS patients and healthy subjects. Furthermore, IL-1β levels were higher in MS patients compared to healthy EBV carriers. MTT assay revealed no significant difference in cell viability between the two groups. DISCUSSION: The higher levels of IL-1β in response to EBV antigens in MS patients may reflect the host neuroinflammatory environment and support the notion that immune response against EBV has a role as an aggravating factor in the progression of MS by contributing to the neuroinflammatory cascade.

Low Risk of Serological Cross-Reactivity between the Dengue Virus and SARS-CoV-2-IgG Antibodies Using Advanced Detection Assays.

Shurrab FM, Al-Sadeq DW, Amanullah FH … +5 more , Al-Absi ES, Qotba H, Yassine HM, Abu-Raddad LJ, Nasrallah GK

Intervirology · 2022 · PMID 35134813 · Full text

Several studies have reported serological cross-reactivity of the immune responses between SARS-CoV-2 and DENV. Most of the available studies are based on the point-of-care rapid testing kits. However, some rapid test ki... Several studies have reported serological cross-reactivity of the immune responses between SARS-CoV-2 and DENV. Most of the available studies are based on the point-of-care rapid testing kits. However, some rapid test kits have low specificity and can generate false positives. Hence, we aimed to investigate the potential serological cross-reactivity between SARS-CoV-2 and DENV-IgG antibodies using advanced assays including chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) test. A total of 90 DENV-IgG-ELISA-positive and 90 DENV-IgG-ELISA-negative prepandemic sera were tested for anti-SARS-CoV-2-IgG using the automated CL-900i CLIA assay. Furthermore, a total of 91 SARS-CoV-2-IgG-CLIA-positive and 91 SARS-CoV-2-IgG-CLIA-negative postpandemic sera were tested for anti-DENV-IgG using the NovaLisa ELISA kit. The DENV-IgG-positive sera resulted in five positives and 85 negatives for SARS-CoV-2-IgG. Similarly, the DENV-IgG-negative sera also resulted in 5 positives and 85 negatives for SARS-CoV-2-IgG. No statistically significant difference in specificity between the DENV-IgG-positive and DENV-IgG-negative sera was found (p value = 1.00). The SARS-CoV-2-IgG-positive sera displayed 43 positives, 47 negatives, and 1 equivocal for DENV-IgG, whereas the SARS-CoV-2-IgG-negative sera resulted in 50 positives, 40 negatives, and 1 equivocal for DENV-IgG. No statistically significant difference in the proportion that is DENV-IgG positive between the SARS-CoV-2-IgG-positive and SARS-CoV-2-IgG-negative sera (p value = 0.58). In conclusion, there is a low risk of serological cross-reactivity between the DENV and SARS-CoV-2-IgG antibodies when using advanced detection assays.

Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection.

Lee HK, Seo SM, Kim JY … +3 more , Kim HW, Jeong ES, Choi YK

Intervirology · 2022 · PMID 34736262 · Full text

INTRODUCTION: Recombination-activating gene (Rag) 1 and Rag2, which are essential in V(D)J recombination, play a crucial role in B- and T-cell maturation. METHOD: We investigated the effects of Rag2 deficiency in cluster... INTRODUCTION: Recombination-activating gene (Rag) 1 and Rag2, which are essential in V(D)J recombination, play a crucial role in B- and T-cell maturation. METHOD: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. RESULTS: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including macrophage inflammatory protein-1α, induced protein 10, interferon (IFN)-α, IFN-γ, and tumor necrosis factor alpha, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. CONCLUSION: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.

Real-World Single-Center Comparison of the Safety and Efficacy of Entecavir, Tenofovir Disoproxil Fumarate, and Tenofovir Alafenamide in Patients with Chronic Hepatitis B.

Jeong S, Shin HP, Kim HI

Intervirology · 2022 · PMID 34731856 · Full text

INTRODUCTION: Chronic hepatitis B (CHB) is a major cause of chronic liver diseases and tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV) are recommended as primary treatments. This stu... INTRODUCTION: Chronic hepatitis B (CHB) is a major cause of chronic liver diseases and tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV) are recommended as primary treatments. This study aimed to evaluate the efficacy and safety of ETV, TDF, and TAF in a real-world clinical setting. METHODS: In this retrospective cohort study, a total of 363 CHB patients who were treated with ETV (n = 163), TDF (n = 154), or TAF (n = 46) from July 2007 to September 2019 were enrolled. RESULTS: Median patient age was 51 years and 66.4% of patients were male. Median duration of treatment with ETV, TDF, or TAF was 49.0 months (interquartile range, 27.0-74.0 months). In terms of safety, cholesterol was mildly increased in the ETV and TAF groups and significantly lowered in the TDF group than baseline (p < 0.001). There was no significant difference in liver cirrhosis-related complications among the 3 groups at 48 weeks (p = 0.235). Hepatitis B e antigen seroconversion, complete virological response, and alanine aminotransferase normalization at 48 weeks as measures of treatment efficacy were not significantly different among the 3 groups (p = 0.142, 0.538, and 0.520, respectively). There was also no significant difference in cumulative incidence rate of hepatocellular carcinoma (HCC) between the ETV and TDF groups (p = 0.894). CONCLUSIONS: ETV, TDF, and TAF were safe antiviral agents and showed similar antiviral effect for CHB at 48 weeks. Cirrhosis-related complications and annual HCC incidence rates did not differ significantly between the ETV and TDF groups over the 48 week follow-up period.

Hepatitis E Virus Capsid as a Carrier of Exogenous Antigens for the Development of Chimeric Virus-Like Particles.

Lu T, Behloul N, Zhou Y … +5 more , Baha S, Liu Z, Wei W, Shi RH, Meng J

Intervirology · 2022 · PMID 34695827 · Publisher ↗

INTRODUCTION: Virus-like particles (VLPs), self-assembled multiprotein structures, can stimulate robust immune responses due to their structural similarity to native virions that allow the presentation of multiple copies... INTRODUCTION: Virus-like particles (VLPs), self-assembled multiprotein structures, can stimulate robust immune responses due to their structural similarity to native virions that allow the presentation of multiple copies of the target epitopes. Utilizing VLPs as vaccine platforms to present exogenous antigens is a promising and challenging approach in the vaccine development field. This study investigates the potential of the truncated hepatitis E virus (HEV) capsid as a VLP platform to present foreign antigens. METHODS: The S and M domains of the HEV capsid protein were selected as the optimal carrier (CaSM). The exogenous antigen Seq8 containing 3 neutralizing epitopes from 3 different foot-and-mouth disease virus (FMDV) strains was linked to the C-terminal of CaSM to construct a chimeric VLP (CaSM-Seq8). The chimeric particles were produced in Escherichia coli, and their morphology, physicochemical properties, antigenicity, and immunogenicity were analyzed. RESULTS: Morphological analysis showed that CaSM-Seq8 self-assembled into VLPs similar to CaSM VLPs (∼26 nm in diameter) but smaller than native HEV virions. Further, the thermal stability and the resistance to enzymatic proteolysis of Seq8 were enhanced when it was attached to the CaSM carrier. The antigenicity analysis revealed a more robust reactivity against anti-FMDV antibodies when Seq8 was presented on CaSM particles. Upon injection into mice, FMDV-specific IgGs induced by CaSM-Seq8 appeared earlier, increased faster, and maintained higher levels for a longer time than those induced by Seq8 alone or the inactivated FMDV vaccine. CONCLUSION: This study demonstrated the potential of utilizing the truncated HEV capsid as an antigen-presenting platform for the development of chimeric VLP immunogens.

Molecular Detection of Parvovirus in Manchurian Chipmunks (Tamias sibiricus asiaticus) Captured in Korea.

Kim JI, Park K, Shin H … +2 more , Choi SM, Song KJ

Intervirology · 2022 · PMID 34695823 · Full text

Cross-species transmission of viral diseases alarms our global community for its potential of novel pandemic events. Of various viral pathogens noted recently, parvoviruses have posed public health threats not only to hu... Cross-species transmission of viral diseases alarms our global community for its potential of novel pandemic events. Of various viral pathogens noted recently, parvoviruses have posed public health threats not only to humans but also to wild animals. To investigate the prevalence of parvoviruses in wild Manchurian chipmunks, here we detected genetic fragments of the nonstructural protein of parvovirus by polymerase chain reaction in wild Manchurian chipmunk specimens captured in the central and southern regions of South Korea and compared their sequence homology with references. Of a total of 348 specimens examined, chipmunk parvovirus (ChpPV)-specific gene fragments were detected with a 31.32% rate (109 chipmunks of 348) in their kidney, liver, lung, and spleen samples, and the chipmunks captured in Gangwon Province exhibited the highest positive rate (45.37%), followed by Gyeongsang (35.29%), Gyeonggi (31.03%), Chungcheong (20.00%), and Jeolla (19.70%). When compared with the reference sequences, a partial ChpPV sequence showed 97.70% identity to the previously reported Korean strain at the nucleic acid level. In the phylogenetic analysis, ChpPV exhibited closer relationship to primate parvoviruses, erythroviruses, and bovine parvovirus than to adeno-associated viruses. Despite limited sample size and genetic sequences examined in this study, our results underline the prevalence of ChpPV in Korea and emphasize the need of close surveillance of parvoviruses in wild animals.

Features of Pathobiology and Clinical Translation of Approved Treatments for Coronavirus Disease 2019.

Fallah A, Razavi Nikoo H, Abbasi H … +3 more , Mohammad-Hasani A, Hosseinzadeh Colagar A, Khosravi A

Intervirology · 2022 · PMID 34666335 · Full text

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently the most important etiological agent of acute respiratory distress syndrome (ARDS) with millions of infections and deaths in the last... BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently the most important etiological agent of acute respiratory distress syndrome (ARDS) with millions of infections and deaths in the last 2 years worldwide. Several reasons and parameters are responsible for the difficult management of coronavirus disease-2019 (COVID-19) patients; the first is virus behavioral factors such as high transmission rate, and the different molecular and cellular mechanisms of pathogenesis remain a matter of controversy, which is another factor. SUMMARY: In the present review, we attempted to explain about features of SARS-COV-2, particularly focusing on the various aspects of pathogenesis and treatment strategies. KEY MESSAGES: We note evidence for the understanding of the precise molecular and cellular mechanisms of SARS-CoV-2 pathogenesis, which can help design the appropriate drug or vaccine. Additionally, and importantly, we reported the updated issues associated with the history and development of treatment strategies such as, drugs, vaccines, and other medications that have been approved or under consideration in clinics and markets worldwide.

Seroprevalence, Genotyping, and Monitoring of Hepatitis C Viral Loads in Patients on Antivirals in Burkina Faso.

Yelemkoure ET, Yonli AT, Sombie HK … +13 more , Tao I, Zouré AA, Ouattara AK, Sorgho AP, Zongo AW, Zeba MTA, Kiendrebeogo IT, Bado P, Kabré MK, Zohoncon TM, Djigma FW, Obiri-Yeboah D, Simpore J

Intervirology · 2022 · PMID 34583364 · Full text

INTRODUCTION: Hepatitis C virus (HCV) infection remains a major public health problem worldwide. In Burkina Faso, nearly 720,000 people are living with HCV, and each year about 900 people die from complications of cirrho... INTRODUCTION: Hepatitis C virus (HCV) infection remains a major public health problem worldwide. In Burkina Faso, nearly 720,000 people are living with HCV, and each year about 900 people die from complications of cirrhosis or hepatocellular carcinoma. This study was planned to determine the HCV seroprevalence, characterize circulating genotypes, and monitor HCV viral loads in patients under treatment with antivirals. METHODS: A total of 4,124 individuals and 167 patients in the pre-therapy program were recruited. The "SD Bioline HCV" kit was used for rapid screening of anti-HCV antibodies. Viral load and genotyping were performed in 167 HCV patients on antivirals using the "Iontek HCV Quant" and "Iontek genotyping" kits. RESULTS: Prevalence of HCV was 1.65% (68/4,124), and the median viral load of participants was 5.37 log10/mL (1.32-7.67 log10/mL). Genotype 2 was predominant with a frequency of 86.23% (144/167) and appeared to be more active with higher viral load compared to 13.77% (23/167) for genotype 1 (p < 0.001). After 24 weeks of pan-genotypic direct-acting antivirals, such as sofosbuvir/daclatasvir and sofosbuvir/velpatasvir, the viral loads of all patients became undetectable. CONCLUSION: The responses to antivirals by the circulating genotypes indicate that the results are very satisfactory. Therefore, the prevalence of HCV in the population can be reduced through identification of cases and treatment.

Adverse Events following AstraZeneca COVID-19 Vaccine in Saudi Arabia: A Cross-Sectional Study among Healthcare and Nonhealthcare Workers.

Alghamdi AA, Alkazemi A, Alissa A … +3 more , Alghamdi I, Alwarafi G, Waggas HA

Intervirology · 2022 · PMID 34544075 · Full text

INTRODUCTION: Many COVID-19 vaccines have been emerging with different efficacy and safety profiles. So far, very little attention has been paid to severity and reactogenicity of COVID-19 vaccine among healthcare workers... INTRODUCTION: Many COVID-19 vaccines have been emerging with different efficacy and safety profiles. So far, very little attention has been paid to severity and reactogenicity of COVID-19 vaccine among healthcare workers. Thus, the aim of this study is to investigate the side effects associated with the first dose of AstraZeneca COVID-19 vaccine among healthcare workers (HCWs) and nonhealthcare workers (non-HCWs). METHOD: This is an observational cross-sectional study conducted at King Abdullah bin AbdulAziz University Hospital, Saudi Arabia, between February 28 and March 12, 2021. The major outcomes were the reported side effects of day 1, day 2, and day 3 after vaccination among HCWs and non-HCWs. Other outcomes included the onset and the duration of the reactions or the side effects that were reported. RESULTS: A total of 526 participants completed the survey with 173 (32.8%) HCWs and the remaining majority were non-HCWs. Some of the most frequently reported side effects among the participants on the first day were muscle aches (49%), followed by fever (42%) and headache (40%). HCWs experienced more muscle aches, headache, sore throat, and abdominal pain, which were statically significant, compared to non-HCWs. The mean onset of symptoms was 16 (±15.3) h in the HCW arm compared with 12.2 (±10.2) h in non-HCWs (p = 0.0024). Furthermore, the mean duration of symptoms in the HCW group was 37 (±19) h compared with 32.3 (±13) h in the non-HCW group (p = 0.067). CONCLUSION: The reported side effects were common but not pressing in both groups. HCW respondents appeared to have more COVID-19 vaccine-associated symptoms.

Prevalence of Hepatitis B Virus Infection Markers among Patients of the Ibn Sina University Hospital Center (Rabat, Morocco).

Feindiri M, Kabbaj H, El Mzibri M … +4 more , Belkadi B, Bouihat N, Filali-Maltouf A, Seffar M

Intervirology · 2022 · PMID 34518480 · Full text

INTRODUCTION: Viral hepatitis B is a global scourge affecting millions of people worldwide. In Morocco, hepatitis B is considered a public health problem, and available data converge to consider Morocco as a country with... INTRODUCTION: Viral hepatitis B is a global scourge affecting millions of people worldwide. In Morocco, hepatitis B is considered a public health problem, and available data converge to consider Morocco as a country with intermediate endemicity. In the present study, we have planned to evaluate the HBV prevalence in Morocco on a large scale and to assess the prevalence of different serological markers for better management of this infection in Morocco. METHODS: This study was conducted on 18,877 patients referring to the Ibn Sina University Hospital Center of Rabat, Morocco. HBV serological markers including HBsAg, HBsAb, HBeAg, HBeAb, and total HBcAb were assessed by immune-enzymatic assays. The quantification of HBV DNA was performed by real-time PCR. RESULTS: The overall prevalence of positive cases for HBsAg, HBsAb, and total HBcAb was 2.47%, 27.66%, and 21.2%, respectively. From 141 patients with an isolated HBcAb serological profile (HBcAb+/HBsAb-/HBsAg-), HBV DNA was detected in 10 patients, representing a rate of 7.09%. In the present study, up to 95.78% of HBV chronic carriers were negative for HBeAg. CONCLUSION: This study highlights a higher prevalence of HBsAg in the hospital-based population than the general population reported previously in Morocco and a very low HBV immunization coverage. Of particular interest, detectable HBV DNA levels in isolated HBcAb patients show that exclusive HBsAg screening cannot eliminate the risk of HBV transmission in certain cases. Many efforts are then mandatory to promote serological testing and increase the vaccination rate to limit viral dissemination for better management of this disease in Morocco.

HIV-HCV Coinfection: Prevalence and Treatment Outcomes in Malaysia.

Akhtar A, Fatima S, Saeed H … +2 more , Soo CT, Khan AH

Intervirology · 2022 · PMID 34515142 · Publisher ↗

BACKGROUND: Around 130 million infections of hepatitis C virus with 3% overall prevalence are there worldwide. There are approximately 4-5 million persons coinfected with HIV. The main objectives of this study were to de... BACKGROUND: Around 130 million infections of hepatitis C virus with 3% overall prevalence are there worldwide. There are approximately 4-5 million persons coinfected with HIV. The main objectives of this study were to determine the prevalence of HCV among HIV-positive individuals and to assess the predictors involved in the outcomes of HIV-HCV coinfected patients. METHODS: A retrospective, cross-sectional study was conducted on patients enrolled from 2007 to 2012 at Infectious Disease Unit, Hospital Palau Pinang, Pinang, Malaysia. Sociodemographic da%)ta as well as clinical data were collected with the help of a valid data collection form from the patients' records. Data were entered and analyzed by using statistical software SPSS version 20.0, and p < 0.05 was considered significant. RESULTS: The overall prevalence of hepatitis C among 708 HIV-infected patients was 130 (16.1 including 541 (76.4%) males and 167 (23.6%) females. High prevalence of HIV-HCV coinfection was significantly observed in males (122 [17.2%]) compared to females (8 [1.1%]) (p < 0.001). The main route of transmission among HIV-HCV coinfected patients was heterosexual contact (98 [13.8%]), followed by homosexual contact (4 [0.4%]). The statistically significant predictors involved in treatment outcomes of HIV-HCV coinfected patients are gender (OR = 2.015, p = 0.002) and intravenous drug users (OR = 2.376, p ≤ 0.001). CONCLUSION: The current study shows that HCV infection has an impact on the recovery of CD4 cells of the patients on HAART. Screening of HCV among HIV patients who were smokers and intravenous drug users should be monitored before starting HAART.

Low-Intensity Ultrasound as a Novel Strategy to Improve the Cytotoxic Effect of Oncolytic Reovirus on Colorectal Cancer Model Cells.

Sharifi N, Soleimanjahi H, Mokhtari-Dizaji M … +3 more , Banijamali RS, Elhamipour M, Karimi H

Intervirology · 2022 · PMID 34510042 · Publisher ↗

BACKGROUND: Colorectal cancer is the third most common cancer all over the world, so in the battle to fight this hurdle, new therapeutic approaches such as oncolytic viruses (OV) have attracted much attention because of... BACKGROUND: Colorectal cancer is the third most common cancer all over the world, so in the battle to fight this hurdle, new therapeutic approaches such as oncolytic viruses (OV) have attracted much attention because of the fact that they can inherently kill cancer cells. Oncolytic reovirus is one of the candidates for treatment as a nonpathogenic species specially reovirus type 3 Dearing (T3D), which can induce apoptosis. To speed up the entry and function of the reovirus, low-intensity ultrasound, which is a safe system for damage to the cells and tissues, is a promising approach to be used in combination with other therapeutic approach. METHODS: L929 and CT26 cells were infected with reovirus T3D and were exposed to ultrasonic irradiation (1 MHz, 1 W/cm2, and 20% duty factor) for 10 s. The viruses' titer level of both groups was calculated in 2 types of cells by using the CCID50 method and compared with each other. Apoptosis, after 24 h, was measured by the flow cytometry method. RESULT: The results of CCID50 in infected cells were exposed to low-intensity ultrasound showed an increased virus titer compared with unexposed infected cells. Moreover, according to the results of the flow cytometry test, it was found that the amount of apoptosis in infected cells that are exposed to low-intensity ultrasound waves is higher than those infected cells. CONCLUSION: Due to the results of CCID50 and flow cytometry tests, low-intensity ultrasound increases the cytotoxicity level of reovirus in CT26 cells of the cellular colorectal cancer model.

Updating on Roles of HIV Intrinsic Factors: A Review of Their Antiviral Mechanisms and Emerging Functions.

Hadpech S, Moonmuang S, Chupradit K … +2 more , Yasamut U, Tayapiwatana C

Intervirology · 2022 · PMID 34464956 · Full text

BACKGROUND: Host restriction factors are cellular proteins that inhibit specific steps of the viral life cycle. Since the 1970s, several new factors have been identified, including human immunodeficiency virus-1 (HIV-1)... BACKGROUND: Host restriction factors are cellular proteins that inhibit specific steps of the viral life cycle. Since the 1970s, several new factors have been identified, including human immunodeficiency virus-1 (HIV-1) replication restriction. Evidence accumulated in the last decade has substantially broadened our understanding of the molecular mechanisms utilized to abrogate the HIV-1 life cycle. SUMMARY: In this review, we focus on the interaction between host restriction factors participating in the early phase of HIV-1 infection, particularly CA-targeting proteins. Host factors involved in the late phase of the replication cycle, such as viral assembly and egress factors, are also described. Additionally, current reports on well-known antiviral intrinsic factors, as well as other viral restriction factors with their emerging roles, are included. CONCLUSION: A comprehensive understanding of the interactions between viruses and hosts is expected to provide insight into the design of novel HIV-1 therapeutic interventions.

Emergence of a Novel Reassortant H5N3 Avian Influenza Virus in Korean Mallard Ducks in 2018.

Yeo SJ, Hoang VT, Duong TB … +5 more , Nguyen NM, Tuong HT, Azam M, Sung HW, Park H

Intervirology · 2022 · PMID 34438407 · Full text

INTRODUCTION: The avian influenza (AI) virus causes a highly contagious disease which is common in wild and domestic birds and sporadic in humans. Mutations and genetic reassortments among the 8 negative-sense RNA segmen... INTRODUCTION: The avian influenza (AI) virus causes a highly contagious disease which is common in wild and domestic birds and sporadic in humans. Mutations and genetic reassortments among the 8 negative-sense RNA segments of the viral genome alter its pathogenic potential, demanding well-targeted, active surveillance for infection control. METHODS: Wild duck fecal samples were collected during the 2018 bird health annual surveillance in South Korea for tracking variations of the AI virus. One low-pathogenic avian influenza H5N3 reassortment virus (A/mallard duck/South Korea/KNU18-91/2018 [H5N3]) was isolated and genomically characterized by phylogenetic and molecular analyses in this study. RESULTS: It was devoid of polybasic amino acids at the hemagglutinin (HA) cleavage site and exhibited a stalk region without deletion in the neuraminidase (NA) gene and NA inhibitor resistance-linked E/D627K/N and D701N marker mutations in the PB2 gene, suggesting its low-pathogenic AI. It showed a potential of a reassortment where only HA originated from the H5N3 poultry virus of China and other genes were derived from Mongolia. In phylogenetic analysis, HA was different from that of the isolate of H5N3 in Korea, 2015. In addition, this novel virus showed adaptation in Madin-Darby canine kidney cells, with 8.05 ± 0.14 log10 50% tissue culture infectious dose (TCID50) /mL at 36 h postinfection. However, it could not replicate in mice well, showing positive growth at 3 days postinfection (dpi) (2.1 ± 0.13 log10 TCID50/mL) but not at 6 dpi. CONCLUSIONS: The HA antigenic relationship of A/mallard duck/South Korea/KNU18-91/2018 (H5N3) showed differences toward one of the old low-pathogenic H5N3 viruses in Korea. These results indicated that a novel reassortment low-pathogenic avian influenza H5N3 subtype virus emerged in South Korea in 2018 via novel multiple reassortments with Eurasian viruses, rather than one of old Korean H5N3 strains.

The Regulation of Prototype Foamy Virus 5'Long Terminal Repeats and Internal Promoter by Endogenous Transcription Factors.

Wei J, Sun Y, Wang TT … +4 more , Zhu G, Liu WH, He XH, Li Z

Intervirology · 2022 · PMID 34438397 · Full text

BACKGROUND: For foamy virus, the transactivator of spumaretrovirus (Tas) could bind directly to target DNA sequences termed as Tas responsive elements and trigger the viral internal promoter (IP) and long terminal repeat... BACKGROUND: For foamy virus, the transactivator of spumaretrovirus (Tas) could bind directly to target DNA sequences termed as Tas responsive elements and trigger the viral internal promoter (IP) and long terminal repeat (LTR) promoters. The cellular endogenous factors also play an important role in viral gene expressions. We hypothesized that except the viral transcription factor Tas, the cellular endogenous factors also affect the viral gene expression. METHODS: The full length of the prototype foamy virus (PFV) genome (U21247) was used to predict the potential binding sites of the transcription factors by online software JASPAR (http://jaspar.genereg.net) and Softberry (http://linux1.softberry.com/berry.phtml?topic=index&amp;group=programs&amp;subgroup=promoter). The Dual-Luciferase® Reporter Assay System (Promega, USA) was used to confirm the relative luciferase activities of the test groups. The different representative activating agents or inhibitors of each canonical signal pathway were used to identify the impact of these pathways on PFV 5'LTR and IP promoters. RESULTS: The results showed different cellular endogenous factors might have respective effects on PFV 5'LTR and IP. It is worth mentioning that activator protein-1 and BCL2-associated athanogene 3, 2 kinds of vital proteins associated with NF-κB and PKC pathways, could activate the basal activity of 5'LTR and IP promoters but inhibit the Tas-regulated activity of both promoters. Furthermore, PFV Tas was identified to trigger the transcription of the NF-κB promoter. CONCLUSION: NF-κB had a negative effect on PFV 5'LTR and IP promoter activities, the PKC pathway might upregulate 5'LTR and IP promoter activities, and the JNK and NF-AT signal pathway could increase the Tas-regulated promoter activity of PFV 5'LTR. This study sheds light on the interaction between PFV and the host cell and may help utilize the viral promoters in retroviral vectors designed for gene transfer experiments.

Human Herpesvirus 6 Infection and Risk of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis.

Mozhgani SH, Rajabi F, Qurbani M … +9 more , Erfani Y, Yaslianifard S, Moosavi A, Pourrostami K, Baradaran Bagheri A, Soleimani A, Behzadian F, Safavi M, Rezaei F

Intervirology · 2022 · PMID 34348314 · Full text

INTRODUCTION: Chronic fatigue syndrome (CFS) is a neurological disease that is accompanied by excessive fatigue or tiredness. There are several reports confirming the association between human herpesvirus 6 (HHV-6) infec... INTRODUCTION: Chronic fatigue syndrome (CFS) is a neurological disease that is accompanied by excessive fatigue or tiredness. There are several reports confirming the association between human herpesvirus 6 (HHV-6) infection and CFS illness. This systematic review and meta-analysis was performed to integrate the information of published studies with regard to this association until May 2021. METHODS: The literature search was based on keywords including "chronic fatigue syndrome and HHV 6," "chronic fatigue syndrome and HHV-6," "chronic fatigue syndrome and HHV6," "chronic fatigue syndrome and Herpes virus 6," and "chronic fatigue syndrome and Herpesvirus6" in MEDLINE (PubMed), Web of Science, and EMBASE. RESULTS: The literature search identified 17 studies to be included in the systematic review and 11 studies in meta-analysis. The symmetry funnel plot and Egger's test (p value = 0.2) identified no publication bias among studies. Moreover, the low level of I2 revealed homogeneity across studies. DISCUSSION: In conclusion, the association between the HHV-6 infection and CFS incidence was substantiated. However, the results of this study also suggest that further comprehensive studies are needed to solidify the association between HHV-6 and CFS. Future studies should consider additional factors that may have affected the significance of such a correlation.

The Prevalence and Genetic Characterization of Human Metapneumovirus in Bulgaria, 2016-2019.

Korsun NS, Angelova SG, Trifonova IT … +5 more , Voleva SE, Grigorova IG, Tzotcheva IS, Mileva SD, Perenovska PI

Intervirology · 2021 · PMID 34304230 · Full text

INTRODUCTION: We investigated the prevalence of human metapneumovirus (hMPV) among patients with acute respiratory infections in Bulgaria, and performed genetic characterization of the F gene of these strains. METHODS: N... INTRODUCTION: We investigated the prevalence of human metapneumovirus (hMPV) among patients with acute respiratory infections in Bulgaria, and performed genetic characterization of the F gene of these strains. METHODS: Nasopharyngeal swabs collected from patients of a range of ages were tested by using real-time PCR for 12 respiratory viruses. The F gene was sequenced, and phylogenetic and amino acid analyses of the F gene/protein were performed. RESULTS: A total of 1,842 patients were examined during a 3-year period; 1,229 patients (66.7%) were positive for at least one respiratory virus. hMPV was identified in 83 (4.5%) patient samples. Eleven (13%) of hMPV-positive patients were coinfected with another respiratory virus. The hMPV incidence rate in the 2016/2017, 2017/2018, and 2018/2019 winter seasons was 5.4, 5.4, and 3.1%, respectively. hMPV was mainly detected in specimens collected between January and May (89.2% of cases). The incidence of hMPV infection was highest (5.1%) among the youngest age-group (0-4 years), where hMPV was a causative agent in 8.1 and 4.8% of bronchiolitis and pneumonia cases, respectively. Among the patients aged ≥5 years, hMPV was detected in 2.2 and 3.2% of cases of pneumonia and central nervous system infections, respectively. Phylogenetic analysis of the F gene showed that the sequenced hMPV strains belonged to the A2b, B1, and B2 genotypes. Numerous amino acid substitutions were identified compared with the NL00/1 prototype strain. CONCLUSION: This study revealed the significant role of hMPV as a causative agent of serious respiratory illnesses in early childhood, and also demonstrated year-to-year changes in hMPV prevalence and genetic diversity in circulating strains.

Seropositive Reaction Rates of 9 B-Cell Epitopes of the SARS-CoV-2 Spike Protein and the Relationship between the Epitopes and Neutralizing Antibody.

Zhu L, Zhang Y, Yang Z … +9 more , Li B, Feng T, Zou X, He J, He T, Li J, Liu N, Li W, Wang X

Intervirology · 2022 · PMID 34233324 · Full text

OBJECTIVE: The aim of the study was to analyze the relationship between serum antibody and neutralizing antibody titers in convalescent coronavirus disease 2019 (COVID-19) patients with different disease severities, and... OBJECTIVE: The aim of the study was to analyze the relationship between serum antibody and neutralizing antibody titers in convalescent coronavirus disease 2019 (COVID-19) patients with different disease severities, and the seropositive reaction rates of 9 reported B-cell epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Serum IgG and total antibody titers of 165 convalescent COVID-19 patients were determined by chemiluminescence, the serum neutralization antibody titers were determined by microneutralization assay, and the S/CO values of 9 peptides were detected by indirect enzyme-linked immunosorbent assay. Correlations between the aforementioned indexes were statistically analyzed, and differences in patients with different diseases severities were evaluated. RESULTS: IgG, total antibody, and neutralizing antibody titers increased with disease severity. The positive rate of the receptor-binding region (RBD) was 100%, and the average positive rate for all the 9 peptides was above 50% in 165 patients. IDf showed the highest rate of positivity (86.06%), with a rate of 95% for the (IDf + IDa) pattern. Moreover, S/CO values of RBD and mix (IDh) were significantly correlated with IgG, total antibody titers, and neutralizing antibody titers (p < 0.001), whereas the S/CO values for other 8 peptides showed no obvious correlation. CONCLUSION: In this study, a large sample was used to confirm that the peptide IDf had a high positive reaction rate for all patients (86.06%) and also had the highest detection rate in asymptomatic patients (86.67%). Only long peptide and mixed peptide showed correlation with neutralizing antibody titers, suggesting that the ability of SARS-CoV-2 antibody to neutralize virus infectivity may require the interaction of multiple sites.
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