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Intervirology[JOURNAL]

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Challenges and Pragmatic Solutions for Assessing the Reliability of HIV-1 Viral Load Monitoring in Resource-Constrained Settings.

Demosthenes JP, Ghale BC, Alex D … +4 more , Ramalingam VV, Fletcher GJ, Abraham P, Kannangai R

Intervirology · 2024 · PMID 38008075 · Full text

INTRODUCTION: HIV-1 RNA detection is the most reliable method for monitoring treatment response among people living with HIV. Effective quality control measures that include internal quality control (IQC) are challenging... INTRODUCTION: HIV-1 RNA detection is the most reliable method for monitoring treatment response among people living with HIV. Effective quality control measures that include internal quality control (IQC) are challenging in resource-constrained settings. METHODS: We ascertained the utility of the kit low positive control (LPC) as an effective IQC to monitor the reliability of the HIV-1 viral load assay. Variations in LPC values were measured for 390 different runs over 10 years (2011-2021) and compared to in-house IQC data using Levey-Jennings control chart. RESULTS: Overall, the Levey-Jennings analysis showed minimal variation (±0.5 log) for both the LPC and IQC data. The mean LPC value for first 20 runs (20 days) was 2.91. The mean LPC value for the 390 runs comprising 35 different lots was 3.01 ± 0.1 log. CONCLUSION: Our decadal data reveal that Abbott RealTime HIV-1 assay (Abbott Molecular Inc., IL, USA) LPC exhibited no significant biological variation over 390 runs distributed over 10 years. Hence, assay LPC can supplant the IQC for monitoring assay trends as a stable and commutable material in resource-constrained settings.

Comparison of a Multiplex Real-Time PCR Technique with Oxford Nanopore Technologies Next-Generation Sequencing for Identification of SARS-CoV-2 Variants of Concern.

Ahmadi Z, Maleki A, Eybpoosh S … +6 more , Fereydouni Z, Tavakoli M, Kashanian S, Farhan Asadi L, Nemati AH, Salehi-Vaziri M

Intervirology · 2023 · PMID 37812919 · Full text

INTRODUCTION: The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their potential to endangering the global health has increased the demand for a fast-tracking method in compa... INTRODUCTION: The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their potential to endangering the global health has increased the demand for a fast-tracking method in comparison to the next-generation sequencing (NGS) as a gold standard assay, particularly in developing countries. This study was designed to evaluate the performance of a commercial multiplex real-time PCR technique (GA SARS-CoV-2 OneStep RT-PCR Kit, Iran) for identification of SARS-CoV-2 variants of concern (VOCs) compared to the Oxford Nanopore NGS assay. METHODS: A total of 238 SARS-CoV-2-positive respiratory samples from different waves of COVID-19 in Iran were randomly selected in this study. To determine the SARS-CoV-2 VOC, the samples were analyzed via the commercial triple target assay, GA SARS-CoV-2 OneStep RT-PCR Kit, and NGS as well. RESULTS: The results revealed good concordance between GA SARS-CoV-2 OneStep RT-PCR Kit and NGS for identification of SARS-CoV-2 VOCs. GA SARS-CoV-2 OneStep RT-PCR Kit identified Wuhan, Alpha, and Delta variants with 100% relative sensitivity and specificity. Regarding Omicron subvariants of BA.1, BA.2, and BA.4/5, the relative sensitivity of 100%, 100%, and 81.5% and the relative specificity of 95.3%, 93.5%, and 100% were observed. CONCLUSION: Overall, GA SARS-CoV-2 OneStep RT-PCR Kit can be used as a rapid and cost-effective alternative to NGS for identification of SARS-CoV-2 VOCs.

Seroprevalence of Enterovirus D68 Infection among Humans: A Systematic Review and Meta-Analysis.

Shi Y, Ran Q, Wang X … +1 more , Shi L

Intervirology · 2023 · PMID 37793363 · Full text

INTRODUCTION: Human enterovirus D68 (EV-D68), which belongs to enteroviruses of the small RNA family, is a type of enterovirus that can cause acute respiratory tract infection and central nervous system diseases. This st... INTRODUCTION: Human enterovirus D68 (EV-D68), which belongs to enteroviruses of the small RNA family, is a type of enterovirus that can cause acute respiratory tract infection and central nervous system diseases. This study systematically analysed and summarized EV-D68 antibody studies in databases and identified the seropositivity rates of different regions, ages, and sexes. METHODS: Meta-analysis was performed using STATA 16.0 software. I2 and Q tests were used to analyse the heterogeneity of the included studies. Meta-regression analysis was performed for different groups, and Egger's linear regression analysis was used to evaluate publication bias. RESULTS: The results of multiple studies indicated that the serological prevalence range of EV-D68 antibody was 17.78-96.69%. The results of the meta-analysis showed that the seropositivity rate of EV-D68 antibody was 76% (95% confidence interval [CI]: 67-84%), among which that of the Chinese population was 74% (95% CI: 61-86%) and that of other countries was 79% (95% CI: 65-91%). At the same time, a subgroup analysis was conducted. The seroprevalence of EV-D68 antibody was related to age but not sex or region. CONCLUSION: The seropositivity rate was lower in the below 5-year age group; however, it gradually increased with age. The results of this study showed that EV-D68 infection was widespread in the population, and the current clinical infection situation could not reflect the actual epidemic situation of the virus, among which children under 5 years old were vulnerable to infection, which should be given greater attention for epidemic prevention and control.

New Potential MicroRNA Biomarkers in Human Immunodeficiency Virus Elite Controllers, Human Immunodeficiency Virus Infections, and Coinfections with Hepatitis B Virus or Hepatitis C Virus.

Mahmud Hussen B, Noori M, Sayad B … +9 more , Ebadi Fard Azar M, Sadri Nahand J, Bayat M, Babaei F, Karampour R, Bokharaei-Salim F, Mirzaei H, Moghoofei M, Bannazadeh Baghi H

Intervirology · 2023 · PMID 37699384 · Publisher ↗

INTRODUCTION: This research aimed to evaluate the specific microRNA (miRNA) including miR-17-5p, miRN-140-3p miR-191-5p, miR-200c-3p, and miR-N367 and cellular factors (p21, SDF-1, XCL1, CCL-2, and IL-2) in controlling r... INTRODUCTION: This research aimed to evaluate the specific microRNA (miRNA) including miR-17-5p, miRN-140-3p miR-191-5p, miR-200c-3p, and miR-N367 and cellular factors (p21, SDF-1, XCL1, CCL-2, and IL-2) in controlling replication of human immunodeficiency virus (HIV) in ECs. METHODS: The expression of miRNAs was assessed between healthy control groups and patient groups including ART-naïve HIV, HIV ART, ECs, and coinfection (HIV-HBV and HIV-HCV) via real-time PCR technique. Besides, the expression level of the nef gene and cellular factors were assessed by the ELISA method. The differences in the level of cellular factors and selected miRNAs between study groups were analyzed using the Kruskal-Wallis H or one-way ANOVA test. In addition, the potential of selected miRNAs as biomarkers for discriminating study groups was assessed by the receiver-operator characteristic (ROC) curve analysis. RESULTS: Some miRNAs in ECs, HIV ART, and healthy controls have similar expression patterns, whereas a miRNA expression profile of patient groups significantly differed compared to EC and control groups. According to ROC curve analyses, the miR-17-5p, miR-140-3p miR-191-5p, miR-200c-3p, and miR-N367 can be served as biomarkers for discriminating ECs from ART-naïve HIV-infected groups. There was a significant correlation between some miRNAs and cellular factors/the viral load as well. CONCLUSION: This report demonstrated a differentiation in the expression of selected immunological factors and cellular/viral miRNAs in ECs compared to other patient groups. Some miRNAs and cellular factors are involved in the viral replication control, immune response/modulation and can be used as biomarkers for diagnosis of ECs and differentiation with other groups. Differential expression of these miRNAs and cellular factors in different stages of HIV infection can help in finding novel ways for infection control.

Herpes Simplex Virus 1 MicroRNAs: An Update.

Duan Y, Sun L, Li Q

Intervirology · 2023 · PMID 37285807 · Full text

BACKGROUND: Herpes simplex virus 1 (HSV-1), an important human pathogen, is capable of latent infection in neurons and productive (lytic) infection in other tissue cells. Once infected with HSV-1, the immune system of th... BACKGROUND: Herpes simplex virus 1 (HSV-1), an important human pathogen, is capable of latent infection in neurons and productive (lytic) infection in other tissue cells. Once infected with HSV-1, the immune system of the organism cannot eliminate the virus and carries it lifelong. HSV-1 possesses approximately 150 kb of double-stranded linear genomic DNA and can encode at least 70 proteins and 37 mature microRNAs (miRNAs) derived from 18 precursor miRNAs (pre-miRNAs). SUMMARY: These HSV-1-encoded miRNAs are widely involved in multiple processes in the life cycle of the virus and the host cell, including viral latent and lytic infection, as well as host cell immune signaling, proliferation, and apoptosis. KEY MESSAGE: In this review, we focused primarily on recent advances in HSV-1-encoded miRNA expression, function, and mechanism, which may provide new research ideas and feasible research methods systemically and comprehensively.

Impact of Age and Clinico-Biochemical Parameters on Clinical Severity of SARS-CoV-2 Infection.

Wani SA, Gulzar B, Khan MS … +2 more , Majid S, Bhat IA

Intervirology · 2023 · PMID 37263256 · Full text

INTRODUCTION: The surge in novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease-2019 (COVID-19) has overwhelmed the health system. To help health-care workers and po... INTRODUCTION: The surge in novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease-2019 (COVID-19) has overwhelmed the health system. To help health-care workers and policy makers prioritize treatment and to decrease the burden on health systems caused by COVID-19, clinical severity along with various clinico-biochemical parameters was evaluated by designing a cross-sectional study comprising 236 SARS-CoV-2-infected individuals from Kashmir Valley, India. METHODS: Briefly, real-time polymerase chain reaction (RT-PCR) was used for the confirmation of SARS-CoV-2 infection. The principles of spectrophotometry and chemiluminescent microparticle immunoassay (CMIA) were employed to estimate the levels of glucose, TSH, and 25-hydroxy vitamin D levels in serum of infected patients. RESULTS: A total of 236 patients infected with SARS-CoV-2 were taken for this cross-sectional study. Patients with COVID-19 had a male predominance (72.9 vs. 27.1%) and a higher prevalence of 25-hydroxy vitamin D deficiency (72.0 vs. 28.0%) with a mean 25-hydroxy vitamin D levels of 24.0 ± 13.9 in ng/mL. We observed a varied clinical spectrum of SARS-CoV-2 infection with 36.4%, 23.7%, and 29.7% patients having mild, moderate, and severe disease, respectively. We observed that severity of SARS-CoV-2 infection was significantly associated with older age group, hypertension, low TSH levels, and 25-hydroxy vitamin D deficiency. CONCLUSION: We conclude that not only old age but also hypertension and low levels of TSH and 25-hydroxy vitamin D levels could significantly lead to clinical severity of SARS-CoV-2 infection.

Hepatitis C Virus Genotype 5 Variability in Treatment-Naïve Patients in South Africa.

Maunye TK, Gededzha MP, Blackard JT … +2 more , Rakgole JN, Selabe SG

Intervirology · 2023 · PMID 37231989 · Full text

INTRODUCTION: Hepatitis C virus (HCV) genotype 5 was originally identified in South Africa, where it represents 35-60% of all HCV infections. There are limited data on resistance-associated variants (RAVs) in South Afric... INTRODUCTION: Hepatitis C virus (HCV) genotype 5 was originally identified in South Africa, where it represents 35-60% of all HCV infections. There are limited data on resistance-associated variants (RAVs) in South Africa. Thus, we investigated variability within the NS3/NS4A, NS5A, and NS5B genes of treatment-naïve individuals with HCV genotype 5 infection at the Dr. George Mukhari Academic Hospital (DGMAH) in Pretoria, South Africa. METHODS: Nested PCR was performed to amplify the NS3/4A, NS5A, and NS5B genes. RAVs were evaluated using the Geno2pheno tool. RESULTS: In the NS3/4A gene, F56S and T122A were detected in one sample each. The D168E mutation was detected in 7 samples. Within the NS5A gene, the T62M mutation was detected in 2 individuals. In the NS5B gene, 8 of 12 individuals (67%) had the A421V mutation, while all 12 individuals (100%) had the S486A mutation. DISCUSSION: RAVs were detected frequently among treatment-naïve individuals with HCV genotype 5 infection in South Africa. Thus, resistance testing may be prudent when initiating treatment of patients with genotype 5 infection. Additional population-based studies are needed to understand the prevalence of these RAVs during HCV genotype 5 infection.

Evaluation of MicroRNA Expression Pattern (miR-28, miR-181a, miR-34a, and miR-31) in Patients with COVID-19 Admitted to ICU and Diabetic COVID-19 Patients.

Khatami A, Taghizadieh M, Sadri Nahand J … +8 more , Karimzadeh M, Kiani SJ, Khanaliha K, Kalantari S, Chavoshpour S, Mirzaei H, Donyavi T, Bokharaei-Salim F

Intervirology · 2023 · PMID 36882006 · Full text

INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC... INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects. METHODS: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions. RESULTS: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters. DISCUSSION: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.

Clinical Value of Serum miR-106a in the Diagnosis and Prognosis of Human Papillomavirus-Positive Cervical Cancer.

Rao X, Jiang J, Wang Y … +2 more , Ma X, Liu S

Intervirology · 2023 · PMID 36646059 · Full text

INTRODUCTION: Cervical cancer (CC) is a prevailing malignant tumor in women, mainly caused by human papillomavirus (HPV) infection. This study investigated miR-106a expression in the serum of HPV-positive CC patients and... INTRODUCTION: Cervical cancer (CC) is a prevailing malignant tumor in women, mainly caused by human papillomavirus (HPV) infection. This study investigated miR-106a expression in the serum of HPV-positive CC patients and estimated its value in diagnosis and prognosis. METHODS: We enrolled 120 CC patients as study subjects, with another 80 healthy women as controls. Clinical baseline data and clinicopathological indexes including age, tumor size, differentiation degree, FIGO stage, lymph node metastasis, and squamous cell carcinoma antigen (SCC-Ag) were recorded. Serum miR-106a expression was measured using reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve was employed to estimate the efficacy of miR-106a in diagnosing CC or HPV-positive CC. Under a 5-year follow-up, patient survival was recorded, and the impact of miR-106a on overall survival rate was analyzed by the Kaplan-Meier method. The logistic regression model was used to analyze whether miR-106a was an independent prognostic factor for HPV infection in CC patients. RESULTS: Serum miR-106a was upregulated in CC patients and the level >1.365 assisted the CC diagnosis. miR-106a expression in HPV-positive CC patients was elevated relative to HPV-negative CC patients, and serum miR-106a level >1.300 distinguishing HPV positive and HPV negative. HPV positivity was linked with tumor differentiation degree, FIGO stage, lymph node metastasis, and SCC-Ag in CC patients, but not with age and tumor size. High expression of miR-106a in HPV-positive CC patients increased the risk of poor prognosis, and miR-106a expression is an independent prognostic factor for HPV infection in CC patients. CONCLUSION: High expression of miR-106a assists in the diagnosis of HPV-positive CC and predicts poor prognosis.

Broad Antiviral Spectrum of Glycyrrhizic Acid for Human and Veterinary Medicine: Reality or Fiction?

García-Salazar G, Urbán-Morlán Z, Mendoza-Elvira S … +2 more , Quintanar-Guerrero D, Mendoza S

Intervirology · 2023 · PMID 36455522 · Full text

BACKGROUND: Emerging virus infections provoke health problems in people and animals, which generate social and economic issues worldwide. This has spurred the search for new pharmacological strategies to confront them. S... BACKGROUND: Emerging virus infections provoke health problems in people and animals, which generate social and economic issues worldwide. This has spurred the search for new pharmacological strategies to confront them. SUMMARY: The purpose of this review is to draw the reader's attention to pharmacological evaluations of glycyrrhizic acid (GA) and its analogs on the broad range of viruses known in human and veterinary medicine. GA is the main water-soluble constituent extracted from the roots of plants from the genus Glycyrrhiza, commonly known as licorice root. It has long been used due to its broad spectrum of bioactivities, including anti-inflammatory, antiulcer, and antitumor properties. It has also been proposed as an antiviral agent. Medicines derived from GA are currently being used to combat acute and chronic hepatitis and herpes viruses. KEY MESSAGES: This review suggests that GA could be a new broad-spectrum antiviral due to its ability to inhibit DNA or RNA viruses both in vitro and in vivo. GA could be a potential drug for preventing and/or treating various viral diseases.

Porcine Endogenous Retrovirus Induces CXCL10 in Human Monocytes and Monocyte-Derived Primary Cells.

Al-Shehabi H, Bannert N

Intervirology · 2023 · PMID 36382641 · Publisher ↗

INTRODUCTION: Pigs are suitable donor species for xenotransplantation and biological materials from these animals are used for this purpose for many years. A major risk of xenotransplantation is a zoonosis by transspecie... INTRODUCTION: Pigs are suitable donor species for xenotransplantation and biological materials from these animals are used for this purpose for many years. A major risk of xenotransplantation is a zoonosis by transspecies transmission of animal viruses. In this regard, porcine endogenous retroviruses (PERVs) are of paramount importance because some of them are able to infect human cells and could induce innate immune responses. METHODS: Using a replication-competent polytropic PERV-A/C strain, we have analysed the induction of innate immune responses by this virus in human monocytes, monocyte-derived macrophages, and monocyte-derived dendritic cells. RESULTS: PERV-A/C elevates the expression of the C-X-C motif chemokine 10 (CXCL10) up to 1,000-fold in human monocytes and monocyte-derived primary cells. In comparison to CXCL10, the levels of interferon-β (IFN-β) and interferon-stimulated gene 54 (ISG54) were almost unchanged. Heat-inactivated virus did not induce CXCL10 expression. Neither treatment with the reverse transcriptase inhibitors azidothymidine (AZT) and stavudine (d4T) nor treatment with the integrase inhibitor raltegravir (RAL) reduced the activation levels. Furthermore, depletion of SAM domain and HD domain-containing protein 1 (SAMHD1), a restriction factor that blocks PERV-A/C infection at the level of reverse transcription in these myeloid cells, had no significant effect on the CXCL10 induction level. These results imply that innate immune sensing leading to the strong CXCL10 response occurs at an early step of the replication process and does not require products of reverse transcription. Inhibition of Janus kinases (JAKs) by AT9283 prevented the observed CXCL10 induction by the virus, providing evidence that the JAK-STAT signalling pathway is involved in the CXCL10 response in theses myeloid cells. CONCLUSION: Our findings highlight PERVs as inducers of the pro-inflammatory chemokine CXCL10 and other innate immune responses in human monocytes and derived cells with potential implications in the context of xenotransplantation.

Rotavirus Quantification in Children with Acute Gastroenteritis.

Galliano I, Daprà V, Dini M … +4 more , Gavatorta M, Sardo A, Lo Curcio G, Bergallo M

Intervirology · 2023 · PMID 36244340 · Publisher ↗

INTRODUCTION: Most intractable diarrheas are treated with antibiotics, irrespective of the causative agent. This study aimed to quantify rotavirus (RV) with TaqMan real-time PCR in fecal samples of children with acute ga... INTRODUCTION: Most intractable diarrheas are treated with antibiotics, irrespective of the causative agent. This study aimed to quantify rotavirus (RV) with TaqMan real-time PCR in fecal samples of children with acute gastroenteritis (AGE) in accordance with the program of reduction of drug resistance and use of antibiotics. METHODS: A total of 190 fecal specimens were collected from under-5-year-old children with AGE in pediatric Hospital Regina Margherita of Turin in Italy in 2017. A total of 38 out of 67 (56.7%) episodes of AGE were associated with RV genomic detection with a multiplex commercial kit. RESULTS: All fecal specimens were tested for the presence of RV and other GE viruses. The most commonly detected virus was norovirus (41%), astrovirus (15.8%), human bocavirus (8.9%), sapovirus (7.9%), human parechovirus (5.8%), rhinovirus (4.2%), and adenovirus (1%). In 66 out of 190 (34.7%), RV was detectable with the median viral load 7.2E + 11 ± 60E + 11 genomes/mg fecal specimens. DISCUSSION/CONCLUSIONS: Our results showed that RV was present in around 34.7% of children hospitalized for AGE, a rate similar to those reported in previous studies conducted elsewhere which were in the range of 33-75%. Our protocols are able to quantify the absolute number of viral particle/mg of feces. The clinical utility of quantitative molecular assays, such as RV viral load, will be markedly improved.

Relationship of Noncoding RNA and Swine Viruses.

Fang M, Hu W, Deng Z

Intervirology · 2023 · PMID 36220007 · Publisher ↗

BACKGROUND: Swine viruses are well known as a threat to the pig industry. Many signaling pathways and a number of proteins were discovered to participate in the immune responses to swine viruses. Noncoding RNAs (ncRNAs),... BACKGROUND: Swine viruses are well known as a threat to the pig industry. Many signaling pathways and a number of proteins were discovered to participate in the immune responses to swine viruses. Noncoding RNAs (ncRNAs), comprising a different set of transcripts including housekeeping RNAs (for example, rRNAs and tRNAs) and regulatory RNAs (small RNAs and long ncRNAs), recently have been described as important regulators of viral infections regarding swine. SUMMARY: A growing number of studies have shown ncRNAs are an indispensable part in response to virus infection, involved not only in antiviral responses, but in many interactions between host and virus, some of which may benefit the certain types of swine virus. KEY MESSAGES: Here, we review the relationship of ncRNA and viruses through several representative swine viruses. Further, we discuss the potential of using ncRNAs as antiviral biomarkers.

Disinfection Effect of Hexadecyl Pyridinium Chloride on SARS-CoV-2 in vitro.

Chen KD, Ma FK, Wang QJ … +5 more , Wang Y, Zhuang XY, Zhang XN, Mao HY, Zhang YJ

Intervirology · 2023 · PMID 36103866 · Publisher ↗

The novel coronavirus (COVID-19 or 2019-nCoV) is a respiratory virus that can exist in the mouth and saliva of patients and spreads through aerosol dispersion. Therefore, stomatological hospitals and departments have bec... The novel coronavirus (COVID-19 or 2019-nCoV) is a respiratory virus that can exist in the mouth and saliva of patients and spreads through aerosol dispersion. Therefore, stomatological hospitals and departments have become high-infection-risk environments. Accordingly, oral disinfectants that can effectively inactivate the virus have become a highly active area of research. Hexadecyl pyridinium chloride, povidone-iodine, and other common oral disinfectants are the natural primary choices for stomatological hospitals. Therefore, this study investigated the inhibitory effect of hexadecyl pyridinium chloride on severe acute respiratory syndrome coronavirus (SARS-CoV-2) in vitro. Vero cells infected with SARS-CoV-2 were used to determine the disinfection effect; the CCK-8 method was used to determine cytotoxicity, and viral load was determined by real-time PCR. The results showed that hexadecyl pyridinium chloride has no obvious cytotoxic effect on Vero cells in the concentration range of 0.0125-0.05 mg/mL. The in vitro experiments showed that hexadecyl pyridinium chloride significantly inhibits the virus at concentrations of 0.1 mg/mL or above at 2 min of action. Thus, the results provide experimental support for the use of hexadecyl pyridinium chloride in stomatological hospitals.

Effects of Resveratrol on Hepatitis B Virus Replication: In vitro and in vivo Experiments.

Pan P, Li J, Lin W … +1 more , Long G

Intervirology · 2022 · PMID 36088911 · Full text

INTRODUCTION: Hepatitis B virus (HBV) infection is a disease with high incidence and lack of effective treatment. In this study, we further explored the mechanism of resveratrol (RVT) in the inhibition of HBV replication... INTRODUCTION: Hepatitis B virus (HBV) infection is a disease with high incidence and lack of effective treatment. In this study, we further explored the mechanism of resveratrol (RVT) in the inhibition of HBV replication. The effects of RVT on HBV replication were verified using in vitro and in vivo experiments. METHODS: HepG2 and HepG2.2.15 cell lines were cultured in vitro, and different concentrations of RVT were used to determine its effect on the proliferation of the two cell lines. Autophagy agonists and inhibitors were given, and whether RVT exerts its effect on the proliferation of HepG2 and HepG2.2.15 cells through autophagy was determined. Reverse transcription-quantitative polymerase chain reaction and Western blot were used to detect changes in autophagy-related factors LC3-II, LC3-I, Beclin 1, and p62. Through transfection of pmiR-155, shmiR-155, and the corresponding control group, the relevant mechanism of RVT in inhibiting the proliferation of HepG2 and HepG2.2.15 cells was analyzed. RVT inhibited the toxicity for HepG2.2.15 cells and reduced HBV replication in vitro (p < 0.05). This effect of RVT was enhanced by rapamycin (RAPA; autophagy activator; p < 0.05) but was partially reversed by 3-MA (autophagy inhibitor; p < 0.05). In addition, our results showed that miR-155 expression was higher in HepG2.2.15 cells than in HepG cells (p < 0.05). miR-155 expression in the RVT treatment group was significantly reduced (p < 0.05). We designed an miR-155 overexpression plasmid, low miR-155 expression plasmid, and the corresponding negative control for transfection and found that transfection of pmiR-155 can partially reverse the effect of RVT (p < 0.05), while transfection with shmiR-155 can enhance the effect of RVT (p < 0.05). DISCUSSION: RVT inhibits miR-155, activates autophagy, inhibits the toxicity for HepG2.2.15 cells, and reduces HBV replication, providing a new research direction for the treatment of HBV infection.

Molecular Detection and Genotyping of Human Cytomegalovirus in Kidney Transplant Recipients under Ganciclovir Prophylaxis in Iran.

Behnezhad F, Parhizgari N, Shafiei-Jandaghi NZ … +2 more , Yavarian J, Mokhtari-Azad T

Intervirology · 2023 · PMID 35858540 · Full text

INTRODUCTION: Human cytomegalovirus (HCMV) infection is one of the most common viral complications in kidney transplant recipients. Although there are effective treatments strategies for the HCMV infection, this infectio... INTRODUCTION: Human cytomegalovirus (HCMV) infection is one of the most common viral complications in kidney transplant recipients. Although there are effective treatments strategies for the HCMV infection, this infection is still one of the causes of kidney transplant rejection. METHODS: A total of 246 kidney transplant recipients participated in this cross-sectional study. Viral DNA was extracted from these plasma samples, and the presence of HCMV genome was determined by semi-nested PCR with specific primers for the HCMV B glycoprotein gene. Sanger sequencing analyses were carried out to determine HCMV genotypes, and the Mega x software was used for nucleotide alignment and construction of a phylogenetic tree. RESULTS: HCMV DNA was detected in 11 (4.47%) recipients. According to the phylogenetic analysis, HCMV gB3 was 50% among kidney transplant recipients, followed by gB4 30% and gB1 20%; however, the gB2 genotype was not detected. CONCLUSIONS: This study demonstrated that the HCMV infection in our patients is relatively low because all transplant recipients received appropriate prophylaxis, thereby antiviral prophylaxis is recommended for all patients at risk of HCMV infection after kidney transplantation. Also, gB3 was the most predominant genotype among our kidney transplant recipients that was related to the higher rate of prevalence of severe HCMV infections. Moreover, an elevated serum creatinine level was detected in patients at the time of detection of HCMV infection.

Relationship between Human Papillomavirus Prevalence and DNA Damage in Cervical Cancer Population in Gansu Province, China.

Guo Z, Zhu T, Zhou Y … +5 more , Si T, Wang Q, Qu H, Wang C, Zhao J

Intervirology · 2022 · PMID 35820368 · Full text

OBJECTIVES: The aim of this study was to assess the possible reason of the high incidence and mortality of cervical cancer in Longnan, China. MATERIALS AND METHODS: 147 and 124 invasive squamous-cell carcinoma (SCC) samp... OBJECTIVES: The aim of this study was to assess the possible reason of the high incidence and mortality of cervical cancer in Longnan, China. MATERIALS AND METHODS: 147 and 124 invasive squamous-cell carcinoma (SCC) samples from Longnan and different cities and districts of Gansu province were collected in the present study. All the samples were obtained from patients who underwent biopsies with colposcopy or advanced operations and were evaluated by experienced pathologists. HPV genotypes were examined with a validated HPV subtypes kit. The prevalence of HPV infection in SCC patients of China was analyzed by evidence-based medicine in the published literature. The markers of DNA damage response (DDR) - ATMpSer1981, H2AXp Ser139 (γH2AX), Chk2pThr68, and p53 - were analyzed by immunohistochemistry. RESULTS: HPV positivity, high-risk and multiple HPV positivity, and HPV58 infection were significantly higher in Longnan. Our results show that the prevalence of HPV infection in SCC patients of Longnan are consistent with the HPV prevalence in China. ATM, γH2AX, and p53 expressions in total and HPV+ samples were also higher in Longnan. CONCLUSIONS: HPV-related DDR activation may be one reason for the high incidence and mortality of Longnan cervical cancer.

Identification and Verification of Ubiquitin D as a Gene Associated with Hepatitis C Virus-Induced Hepatocellular Carcinoma.

Li H, Liu S, Lin Y … +6 more , Shi X, Du N, Yao J, Liu R, Du Y, Yang K

Intervirology · 2022 · PMID 35728518 · Full text

INTRODUCTION: Accumulated studies have suggested that hepatitis C virus (HCV) infection is one of the leading causes for hepatocellular carcinoma (HCC). However, the mechanisms underlying the effect of HCV on the occurre... INTRODUCTION: Accumulated studies have suggested that hepatitis C virus (HCV) infection is one of the leading causes for hepatocellular carcinoma (HCC). However, the mechanisms underlying the effect of HCV on the occurrence of HCC are still poorly understood. METHODS: HCV infection datasets (GSE82177 and GSE17856) and HCC datasets (The Cancer Genome Atlas Liver Hepatocellular Carcinoma and GSE89377) were downloaded from Gene Expression Omnibus or TCGA for analysis. The common differentially expressed genes in the above four datasets were identified by R software. The expression of ubiquitin D (UBD) in HCV-infected HepG2 cells was detected by RT-qPCR and Western blot, respectively. The interaction between NS3 and p53 was detected by co-immunoprecipitation. The influence of UBD on the proliferation and migration ability of HepG2 cells was evaluated by CCK-8 and wound healing assay, respectively. RESULTS: UBD was upregulated in both HCV-infected samples and HCC samples. HCV NS3 interacted with p53 and inhibited its expression. HCV NS3-induced UBD promoted the proliferation and migration of HepG2 cells. CONCLUSION: Our results suggest that HCV NS3-induced UBD is positively correlated with the development of HCV-related HCC during HCV infection. Targeting UBD could be a potential strategy for preventing and treating HCV-induced HCC.

Incidence of HPVs, EBV, and MMTV-Like Virus in Breast Cancer in Qatar.

Gupta I, Al-Sarraf R, Farghaly H … +5 more , Vranic S, Sultan AA, Al-Thawadi H, Al Moustafa AE, Al-Farsi HF

Intervirology · 2022 · PMID 35640537 · Full text

INTRODUCTION: Human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and mouse mammary tumor virus-like virus (MMTV-like virus) can be present and contribute to breast cancer development and progression. However, the r... INTRODUCTION: Human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and mouse mammary tumor virus-like virus (MMTV-like virus) can be present and contribute to breast cancer development and progression. However, the role of these oncoviruses and their crosstalk in breast cancer is still unclear. METHODS: We explored the co-presence of high-risk HPVs, EBV, and MMTV-like virus in 74 breast cancer samples from Qatar using PCR. RESULTS: We found the presence of HPV and EBV in 65% and 49% of our cancer sample cohorts; 47% of the samples are positive for both oncoviruses. The MMTV-like virus alone was detected in 15% of the samples with no significant association with clinicopathological features. The three oncoviruses were co-present in 14% of the cases; no significant association was noted between the co-presence of these viruses and the clinicopathological features. CONCLUSION: Despite the presence of the oncoviruses, additional studies are necessary to understand their interactions in human breast carcinogenesis.

SARS-COV-2 Triggers the Development of Class I and Class II HLA Antibodies in Recovered Convalescent Plasma Donors.

Dada A, Elhassan K, Bawayan RM … +9 more , Albishi G, Hefni L, Bassi S, Sobahy T, Cupler E, AlBaz N, Wali G, Alraddadi B, Alshukairi AN

Intervirology · 2022 · PMID 35378533 · Full text

Various studies have shown that SARS-CoV-2 is a highly immunogenic virus. It is known that different types of immunogenic viral pathogens could trigger the formation of HLA antibodies. Therefore, there is a concern that... Various studies have shown that SARS-CoV-2 is a highly immunogenic virus. It is known that different types of immunogenic viral pathogens could trigger the formation of HLA antibodies. Therefore, there is a concern that the SARS-CoV-2 could also induce the development of HLA antibodies in volunteers, who donate convalescent plasma after their recovery from COVID-19. HLA antibodies have been identified as the main cause for transfusion-related acute lung injury (TRALI), a well-documented life-threatening complication of transfusions. The TRALI risk could be high in COVID-19 patients who need convalescent plasma, as such patients usually have already an impaired respiratory system affected by the SARS-CoV-2 infection. In this study, we screened 34 convalescent plasma donors on the presence of antibodies against HLA class I and II antigens. All included donors have no any history of sensitization events such as blood transfusions, pregnancy, or previous transplants. We found a high rate of HLA antibody formation in convalescent plasma donors. The frequency of positivity for HLA antibodies for class I, class II, class I and II, and the overall reactivity was 23%, 31%, 46%, and 76%, respectively. The presented data suggest a closed correlation between SARS-CoV-2 virus infection and the development of HLA antibodies in recovered convalescent plasma donors. This finding might have the potential to reduce the risk of TRALI and mortality rate in COVID-19 patients by implementing HLA diagnostic strategies before the administration of convalescent plasma.
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