Intervirology[JOURNAL]
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200 papers
E3 Gene-Based Genetic Characterization of Canine Adenovirus-2 Isolated from Cases of Canine Gastroenteritis in India Revealed a Novel Group of the Virus.
Ramidi A, Ganji VK, Buddala B … +3 more , Yella NR, Manthani GP, Putty K
Intervirology · 2019 · PMID 32259812 · Publisher ↗
Canine adenovirus (CAV) circulates as two distinct serotypes, CAV-1 and CAV-2, which are antigenically related but differ in their clinical manifestations. CAV is one of the important viral agents in the etiology of cani...
Canine adenovirus (CAV) circulates as two distinct serotypes, CAV-1 and CAV-2, which are antigenically related but differ in their clinical manifestations. CAV is one of the important viral agents in the etiology of canine gastroenteritis. Here, we report the molecular surveillance and genetic characterization of CAV from clinical cases of canine gastroenteritis. A total of 302 fecal/rectal swabs were collected from dogs presented with gastroenteritis at various clinics in and around Hyderabad, India during 2018-19. These samples were tested for CAV using polymerase chain reaction with primers designed for the CAV E3 gene and the virus was isolated from positive samples. CAV-2 nucleic acid was present in 4.9% of the test samples. The partial sequence analyses of the E3 gene of the CAV-2 isolates revealed a frameshift mutation by insertion of nucleotide "G" at 1077 position of E3 gene, which resulted in an extension of the polypeptide chain by eleven amino acids. As a result, isolates from the current study formed a novel group, and the virus that was previously subdivided into two groups worldwide is now categorized under three. The study identifies a novel group of CAV-2 circulating in India providing an updated information regarding CAV-2.
Seroprevalence of Human Cytomegalovirus in Pregnant Women in the Asir Region, Kingdom of Saudi Arabia.
Almaghrabi MK, Alwadei AD, Alyahya NM … +7 more , Alotaibi FM, Alqahtani AH, Alahmari KA, Alqahtani MS, Alayed AS, Moosa R, Ali AS
Intervirology · 2019 · PMID 32208395 · Full text
BACKGROUND: Human cytomegalovirus (HCMV) infection spreads easily by interpersonal contact. OBJECTIVE: This study determined the prevalence of seropositivity of cytomegalovirus immunoglobulin G (IgG) in the Asir Region,...
BACKGROUND: Human cytomegalovirus (HCMV) infection spreads easily by interpersonal contact. OBJECTIVE: This study determined the prevalence of seropositivity of cytomegalovirus immunoglobulin G (IgG) in the Asir Region, Kingdom of Saudi Arabia. METHODS: The study evaluated the seropositivity for cytomegalovirus-specific IgG in 460 females. Collected samples were processed and tested using enzyme-linked immunosorbent assay and specific HCMV IgG. RESULTS: The study showed that all the respondents aged 15-20 years were seropositive for the HCMV. HCMV seropositive status was recorded in 99.2% of the older patients (>40 years of age). In the remaining age groups, the rate of seropositivity ranged from 95.7 (age range 20-25 years) to 98.9% (age range 30 years). CONCLUSIONS: In all age groups of females tested, the prevalence of seropositive for HCMV was high, i.e., in the range of 95.7-100%.
Detection of Human Papillomavirus Prevalence in Ovarian Cancer by Different Test Systems.
Kisseljova N, Zhordania K, Fedorova M … +6 more , Katargin A, Valeeva A, Pajanidi J, Pavlova L, Khvan O, Vinokurova S
Intervirology · 2019 · PMID 32088719 · Publisher ↗
BACKGROUND/AIMS: High-risk human papillomavirus (HPV) infection is associated with different malignancies, but its role in the pathogenesis of ovarian cancer remains inconclusive. Published studies demonstrated a wide va...
BACKGROUND/AIMS: High-risk human papillomavirus (HPV) infection is associated with different malignancies, but its role in the pathogenesis of ovarian cancer remains inconclusive. Published studies demonstrated a wide variation (0-50%) in HPV prevalence in ovarian cancer. To evaluate the contribution of detection tests to controversial results in different populations, we determined the presence of HPV DNA in Russian ovarian cancer patients using 10 different PCR-based tests. METHODS: Epithelial ovarian adenocarcinomas were tested with 5 general primer sets commonly used for HPV screening of cervical and ovarian cancer and 5 HPV type-specific primers. RESULTS: The use of a single PCR primer set resulted in a wide variation (0-29%) and an underestimation of the incidence of HPV-positive cancers. The combination of MY09/MY11 and GP5+/6+ primers in nested PCR revealed HPV DNA in 53% (18/34) of adenocarcinomas. HPV16 was found in 94% of the HPV-positive cases. In 6/6 positive cases, the active status of HPV16 was demonstrated by RT-PCR detection of E6 and E7 oncogene mRNAs. CONCLUSION: These findings indicate the need to employ multiple PCR-based tests to detect all HPV-positive patients. The identification of viral DNA and oncogene transcripts in cancerous tissues indicate the possible role of HPV in ovarian carcinogenesis in Russia.
Variation in Hepatitis C Virus Subtype Distribution during 20 Years in Venezuela.
Loureiro CL, Jaspe RC, Pujol FH
Intervirology · 2019 · PMID 31865350 · Publisher ↗
OBJECTIVE: Hepatitis C virus (HCV) infection is a public health problem and a major cause of chronic hepatitis. This virus exhibits a great genetic variability, with 8 genotypes and numerous subtypes. The aim of this stu...
OBJECTIVE: Hepatitis C virus (HCV) infection is a public health problem and a major cause of chronic hepatitis. This virus exhibits a great genetic variability, with 8 genotypes and numerous subtypes. The aim of this study was to evaluate the fluctuations of HCV subtypes during 2 decades in Venezuela. METHODS: HCV genotypes were determined by direct sequencing of the 5'-noncoding region in 392 isolates circulating in patients attended during the years 2014-2015. HCV subtype assignment was confirmed in a subset of samples (n = 24) by partial sequencing of the NS5B region. The genotype distribution was compared with the one observed in a previous study of patients followed up during the years 1994-1996 and 2005-2006. RESULTS: Some variation was observed in the HCV genotype distribution over these 20 years. HCV genotype 1b prevalence was reduced significantly from 1994-1995 to 2004-2005, as previously described, and then remained constant. During the last 10 years, a significant decrease of HCV subtype 2b (36/237 in 2005-2006 vs. 24/392 in 2014-2015, p < 0.001) was observed. Patients infected with HCV G2acj were significantly older than the ones infected with G1 (53 vs. 47 years, p = 0.004), and male sex was significantly more prevalent among G3a-infected patients compared to the other ones (71 vs. 47%, p = 0.047). CONCLUSIONS: Fluctuations in HCV subtype distribution have been observed over 2 decades in Venezuela. Different major mode of transmission and susceptibility to the available HCV treatment during each period might be playing a role in the observed fluctuations in HCV subtype distribution.
The Influence of Antiretroviral Therapy on Hepatitis C Virus Viral Load and Liver Fibrosis in Human Immunodeficiency Virus-Coinfected Patients: An Observational Study.
Soares J, Ferreira A, Silva-Pinto A … +4 more , Almeida F, Piñeiro C, Serrão R, Sarmento A
Intervirology · 2019 · PMID 31775148 · Publisher ↗
BACKGROUND: The role of antiretroviral therapy (ART) for Hepatitis C viral load (HCV-VL) and liver fibrosis is poorly understood. This study aimed at evaluating the influence of ART on HCV-VL and liver fibrosis in human...
BACKGROUND: The role of antiretroviral therapy (ART) for Hepatitis C viral load (HCV-VL) and liver fibrosis is poorly understood. This study aimed at evaluating the influence of ART on HCV-VL and liver fibrosis in human immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We conducted a retrospective cohort study of HIV/HCV-coinfected patients followed at a tertiary university hospital. RESULTS: In total, 143 patients were included. In 61 patients, ART initiation was accompanied by an increase in HCV-VL and a decrease in HIV viral load (HIV-VL), whereas ART suspension led to a decrease in HCV-VL and an increase in HIV-VL. Among the 55 HIV-suppressed patients who switched to a raltegravir (RAL)-containing regimen, median HCV-VL levels decreased significantly, while switching to a rilpivirine-containing regimen did not yield a significant reduction. DISCUSSION: If the -treatment of chronic hepatitis starts before ART, ART initiation should be delayed as much as possible. If ART has been started, it is advisable to wait 1 year before initiating chronic hepatitis treatment. RAL as the third agent in an ART regimen could be beneficial in HIV/HCV-coinfected patients, in comparison to other antiretroviral drugs. CONCLUSION: The start and the suspension of ART significantly interferes with HCV-VL in HIV/HCV-coinfected patients.
An Outbreak of Human Parainfluenza Virus 3 (Phylogenetic Subcluster C5) Infection among Adults at a Residential Care Facility for the Disabled in Croatia, 2018.
Civljak R, Kosutic-Gulija T, Slovic A … +5 more , Huljev E, Turcic N, Mestrovic T, Vranes J, Ljubin-Sternak S
Intervirology · 2019 · PMID 31661701 · Publisher ↗
INTRODUCTION: Although highly pertinent for children, outbreaks of human parainfluenza virus (HPIV) may cause up to 15% of all respiratory illnesses in adults and predispose them to serious adverse outcomes, with HPIV se...
INTRODUCTION: Although highly pertinent for children, outbreaks of human parainfluenza virus (HPIV) may cause up to 15% of all respiratory illnesses in adults and predispose them to serious adverse outcomes, with HPIV serotype 3 (HPIV3) being the most common. This study represents the first report of an HPIV3 outbreak among adults at a long-term health-care facility in Croatia. METHODS: A retrospective study was conducted to investigate an outbreak of acute respiratory infection (ARI) at a single residential care facility for the disabled in Croatia. Demographic, epidemiological, and clinical data were collected for all residents, while hospitalized patients were appraised in detail by laboratory/radiological methods. Multiplex PCR for respiratory viruses and sequencing was performed. Partial HPIV3 HN 581 nt sequences were aligned with HPIV3 sequences from the GenBank database to conduct a phylogenetic analysis, where different bioinformatic approaches were employed. RESULTS: In late June 2018, 5 of the 10 units at the facility were affected by the outbreak. Among the 106 residents, 23 (21.7%) developed ARI, and 6 (26.1%) of them were hospitalized. HPIV3 was identified in 18 (73%) of the residents and 5 (83%) of the hospitalized individuals. Isolated HPIV3 strains were classified within the phylogenetic subcluster C5 but grouped on 2 separate branches of the phylogenetic tree. During the entire outbreak period, none of the institution's employees reported symptoms of ARI. CONCLUSIONS: Our study has shown that this health care-associated outbreak of HPIV3 infection could have been linked to multiple importation events. Preventive measures in curbing such incidents should be enforced vigorously.
Evaluation of Rapid, Molecular-Based Assays for the Detection of Respiratory Syncytial Virus.
Leonardi GP
Intervirology · 2019 · PMID 31542785 · Publisher ↗
OBJECTIVE: Respiratory syncytial virus (RSV) infection causes lower respiratory tract infection primarily in infants and toddlers. RSV reinfection also occurs throughout life and can be a significant cause of pneumonia a...
OBJECTIVE: Respiratory syncytial virus (RSV) infection causes lower respiratory tract infection primarily in infants and toddlers. RSV reinfection also occurs throughout life and can be a significant cause of pneumonia and mortality in the elderly. Surges in physician offices, emergency department visits, and hospitalization often result from RSV illness. Point-of-care (POC) testing reduces healthcare costs and permits informed decisions on treatment, further testing, or hospitalization to occur during the physician-patient encounter. Optimal POC assays must be sensitive, easy to perform, and provide rapid results. METHODS: In this study, 2 POC assays (Alere i; Abbot Rapid Diagnostics and cobas Liat, Roche Molecular, Inc.) and a laboratory-based assay (Solana; Quidel, Inc.) were evaluated using 133 patient nasopharyngeal specimens. RESULTS: Sensitivity/specificity values (%) of 94.7/96.1, 98.2/96.1, and 96.5/94.7 were obtained for the Alere i, Liat, and Solana assays, respectfully. These values approximated those stated in each assay's package insert. CONCLUSION: Rapid molecular assays for RSV are sensitive and accurate. The choice of assay should reflect each healthcare institution's specific testing needs with respect to the benefits and drawbacks of each product.
Differences in Susceptibility of Human and Mouse Macrophage Cell Lines to Respiratory Syncytial Virus Infection.
Heykers A, Leemans A, Van der Gucht W … +3 more , De Schryver M, Cos P, Delputte P
Intervirology · 2019 · PMID 31533107 · Publisher ↗
OBJECTIVES: Differences have been observed in the susceptibility of macrophage cell lines to respiratory syncytial virus (RSV) infection. In this study, we evaluated whether the type of macrophage cell line and RSV strai...
OBJECTIVES: Differences have been observed in the susceptibility of macrophage cell lines to respiratory syncytial virus (RSV) infection. In this study, we evaluated whether the type of macrophage cell line and RSV strain used have an influence on the infectivity and production of progeny virus. METHODS: Both human and murine macrophage-like cell lines were infected with different RSV strains, both lab strains as well as clinical isolates. The infection was evaluated after 24 and 72 h by immunofluorescence staining and microscopic analysis, and the production of new virus particles was determined by plaque assay. RESULTS: Susceptibility of macrophages to RSV was influenced by the RSV strain used but was mostly dependent on the macrophage cell line. Numbers of infected cells and virus production were generally very low or absent in murine cell lines. In human cell lines, clear infection was observed associated with production of new virus particles. CONCLUSION: Differences in susceptibility of macrophage cell lines to RSV infection are primarily related to the species of origin of the cell line but are also influenced by the RSV strain.
Fluorescent Immunosorbent Assay for Chikungunya Virus Detection.
Nguyen HC, Park H, Shin HJ … +9 more , Nguyen NM, Nguyen ATV, Trinh TT, Duong THY, Tuong HT, Hoang VT, Seo GE, Sohn HJ, Yeo SJ
Intervirology · 2019 · PMID 31533104 · Publisher ↗
BACKGROUND: When infected with the chikungunya virus (CHIKV), 3% to 28% of CHIKV-infected individuals remain asymptomatic, necessitating the development of improved high-throughput screening methods to overcome the limit...
BACKGROUND: When infected with the chikungunya virus (CHIKV), 3% to 28% of CHIKV-infected individuals remain asymptomatic, necessitating the development of improved high-throughput screening methods to overcome the limitations of molecular diagnostics or enzyme-linked immunosorbent assays (ELISAs). OBJECTIVE: In this study, two novel monoclonal antibodies (mAbs) targeting envelope 1 (E1) of CHIKV were developed and applied in a fluorescence-linked immunosorbent assay (FLISA) using coumarin-derived dendrimer as the fluorophore. METHODS: The performance of the FLISA was compared with that of ELISA. RESULTS: Using the two novel mAbs (2B5 and 2C8), FLISA could detect 1 × 105 PFU/mL of CHIKV, exhibiting a 2-fold lower limit of detection (LOD) compared to ELISA. The LOD of FICT corresponded to a comparative threshold value of 23.95 and 4 × 106 of RNA copy number/µL. In the presence of human sera and blood, virus detection by FLISA was 3-fold better than ELISA, with an LOD of 2 × 105 PFU/mL. Sera and blood interfered with the ELISA, resulting in 6 × 105 PFU/mL as the LOD. CONCLUSIONS: FLISA using two novel mAbs and coumarin-derived dendrimer is a superior diagnostic assay for detecting CHIKV in human sera and blood, compared to conventional ELISA.
A Meta-Analysis on Human Papillomavirus Type Distribution among Women with Cervical Neoplasia in the WHO Eastern Mediterranean Region.
Shoja Z, Farahmand M, Hosseini N … +1 more , Jalilvand S
Intervirology · 2019 · PMID 31527382 · Publisher ↗
INTRODUCTION: To date, the human papillomavirus (HPV) vaccine has not been integrated into the national vaccination program of most countries of the WHO Eastern Mediterranean Region (EMRO), except for the United Arab Emi...
INTRODUCTION: To date, the human papillomavirus (HPV) vaccine has not been integrated into the national vaccination program of most countries of the WHO Eastern Mediterranean Region (EMRO), except for the United Arab Emirates and Libya. The knowledge of HPV genotype distribution in cervical neoplasia is valuable to predict the impact of current HPV vaccines on cancer prevention and can help the health policymakers to select the most appropriate vaccine types in their countries. METHODS: Hence, this meta-analysis recapitulates all available data on HPV prevalence and genotypes in women with atypical squamous cells of undetermined significance (ASCUS), cervical intraepithelial neoplasia (CIN) I-III or low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), and invasive cervical cancer (ICC) in EMRO countries. RESULTS: The meta-analysis included 5,990 cases of cervical precancer and cancer. The overall HPV prevalence was 85.4, 71.3, 59.2, and 34.8% in women with ICC, CIN II-III or HSIL, CIN I or LSIL, and ASCUS, respectively. HPV 16 was the most common genotype followed by HPV 18, representing 58 and 16.5% in ICC cases, respectively. CONCLUSION: This meta-analysis showed that the introduction of current HPV vaccines into national vaccination programs and the establishment of comprehensive screening programs in EMRO countries is beneficial by preventing 74.5% of cervical neoplasia.
Analytical Evaluation of the Human Papillomavirus HPV DNA Array E1-Based Genotyping Assay.
Pesic A, Krings A, Schreckenberger C … +3 more , Hempel M, Preyer R, Kaufmann AM
Intervirology · 2019 · PMID 31487743 · Full text
BACKGROUND: Cervical cancer is caused by a persistent infection of human papillomavirus (HPV). Therefore, tests which detect the carcinogenic virus can be used for cervical cancer screening. OBJECTIVE: This is the first...
BACKGROUND: Cervical cancer is caused by a persistent infection of human papillomavirus (HPV). Therefore, tests which detect the carcinogenic virus can be used for cervical cancer screening. OBJECTIVE: This is the first evaluation of the HPV DNA Array (AID Diagnostika, Strassberg, Germany), an E1-based genotyping polymerase chain reaction (PCR) test for identification of 29 HPV types (6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, 85, and 97). METHODS: Analytical performance of the assay was assessed with cervical cancer cell lines with known HPV status, and preselected clinical cervical scrapings genotyped by multiplexed genotyping (MPG) with a Luminex readout (validated in-house assay). Intra- and inter-laboratory reproducibility experiments were performed to ensure the reliability of the assay. RESULTS: HPV DNA Array identified the intrinsic HPV genotype in all cervical cancer cell lines and demonstrated a high sensitivity for HPV16 probe (1 cell per PCR reaction), as well as HPV18 and 45 probes (100 cells per PCR reaction). When compared with MPG, HPV DNA Array showed a good agreement of 92.2% for HPV detection irrespective of type (κ = 0.601), and demonstrated high agreement for HPV16 (80.7%, κ = 0.836) and HPV18 (86.7%, κ = 0.925). Furthermore, high intra-/inter-laboratory reproducibility was observed (90.9-100%). CONCLUSION: HPV DNA Array showed high sensitivity for correct HPV genotype detection in experimental and clinical samples with a good correlation to the reference test. Since HPV DNA Array is based on a simple multiplexed PCR followed by reverse hybridization in a 96-well format and automated visual readout by AID ELISpot reader, it is capable of high throughput in a time-effective manner. HPV DNA Array could be considered for extended HPV genotyping of cervical smears.
The Use of Immunochromatographic Technique for Rotavirus Detection: Experience from a Tertiary Care Hospital in Central Greece.
Vontas A, Hadjicristodoulou C, Krikelis V … +1 more , Petinaki E
Intervirology · 2019 · PMID 31487720 · Publisher ↗
Despite the significant medical advances which have taken place in the last decades, acute diarrhoea cases remain a public health issue of major significance, with gastroenteritis agents being associated with severe symp...
Despite the significant medical advances which have taken place in the last decades, acute diarrhoea cases remain a public health issue of major significance, with gastroenteritis agents being associated with severe symptoms in adults and high morbidity in infants and children. Regarding rotaviruses, while children are the predominant victims of rotavirus infection, adults (often caretakers or parents of these children) may experience the same symptoms of fever, vomiting, and non-bloody diarrhoea. Three different routine schemes for the detection of rotaviruses in archived stool samples were evaluated in terms of diagnostic performance. A total of 640 archived stool samples were included in the study. The samples were screened with three different techniques: a commercial rapid immunochromatographic test, a modified in-house conventional one-step reverse-transcription polymerase chain reaction (PCR) screen protocol, and a com-mer-cial one-step real-time PCR kit. Technical aspects and considerations are discussed.
The Long-Noncoding RNA lnc-NONH Enhances the Early Transcription of Prototype Foamy Virus Via Upregulating Expression of miR-34c-5p and Tas Protein.
Xu S, Yang W, Yuan P … +11 more , Yan J, Tang Y, Zheng Y, Li Z, Sun Y, Han S, Yin J, Peng B, He X, Pan Q, Liu W
Intervirology · 2019 · PMID 31430761 · Publisher ↗
BACKGROUND: Prototype foamy virus (PFV) is a complex and unique retrovirus with the longest genome among the retroviruses and is used as a vector for gene therapies. The viral Tas protein transactivates the viral long te...
BACKGROUND: Prototype foamy virus (PFV) is a complex and unique retrovirus with the longest genome among the retroviruses and is used as a vector for gene therapies. The viral Tas protein transactivates the viral long terminal repeat promoter and is required for viral replication. We have utilized RNA sequencing to identify and characterize the long-noncoding RNA NONHSAG000101 (lnc-NONH), which markedly increases in PFV-infected cells. However, little is known about the function of lnc-NONH. OBJECTIVES: We aim to explore the role of lnc-NONH during PFV infection. METHODS: To assess the lnc-NONH role during PFV infection, the siRNAs were used to silence the lnc-NONH expression. The microRNA (miRNA) mimic and inhibitor were employed to explore the function of lnc-NONH-related miRNA miR-34c-5p. Quantitative real-time polymerase chain reaction assay and Western blotting were applied to measure the mRNA and protein levels of PFV transactivator Tas. Luciferase assay was used to determine the transcriptional activity of the PFV unique internal promoter (IP). RESULTS: lnc-NONH promotes the expression of PFV Tas and miR-34c-5p. The interaction between lnc-NONH and miR-34c-5p enhances the transcriptional activity of the PFV IP. CONCLUSIONS: In the current study, we report a novel mechanism for the lnc-NONH-mediated upregulation of Tas expression. Our findings contribute to the understanding of regulatory network of Tas expression and PFV replication.
Apoptosis Induction by Pseudorabies Virus via Oxidative Stress and Subsequent DNA Damage Signaling.
Lai IH, Chang CD, Shih WL
Intervirology · 2019 · PMID 31430757 · Publisher ↗
BACKGROUND: Pseudorabies virus (PRV) infection induces apoptosis in swine cells both in vitro and in vivo; however, the mechanism associated with host-cell signaling has not been studied. This study investigated the role...
BACKGROUND: Pseudorabies virus (PRV) infection induces apoptosis in swine cells both in vitro and in vivo; however, the mechanism associated with host-cell signaling has not been studied. This study investigated the role of free radicals caused by cellular oxidative stress after viral infection and examined whether the DNA damage response plays an important role in PRV-induced apoptosis. METHODS: Several apoptosis assays and western blotting confirmed PRV-induced apoptosis. PRV-mediated oxidative stress was evaluated by reactive oxygen species (ROS) assay. RESULTS: Our results showed that PRV caused apoptosis in a porcine kidney cell line, PK15, and induced expressions of proapoptotic Bcl family proteins in a dose- and time-dependent manner. Expressions of specific DNA damage sensors and phosphorylation of histone H2AX were also significantly increased, which subsequently activated the expressions of checkpoint kinase 1/2 and proapoptotic p53. Caffeine, a known DNA damage inhibitor, was found to inhibit caspase-3 activation and protect cells from PRV-induced apoptosis. Additionally, the antioxidant N-acetyl-L-cysteine was shown to prevent the production of cellular ROS, protecting DNA from cleavage. CONCLUSIONS: Our results confirmed that oxidative stress and free radicals arising from PRV infection cause DNA damage, which consequently triggers apoptosis.
Use of Multiplex Polymerase Chain Reaction for Detection of High-Risk Human Papillomavirus Genotypes in Women Attending Routine Cervical Cancer Screening in Harare.
Marembo T, Dube Mandishora R, Borok M
Intervirology · 2019 · PMID 31412350 · Publisher ↗
BACKGROUND/AIMS: In Zimbabwe, cervical cancer is screened through cytology and visual inspection with acetic acid and cervicography (VIAC). The effectiveness of these methods can be increased if complemented by a human p...
BACKGROUND/AIMS: In Zimbabwe, cervical cancer is screened through cytology and visual inspection with acetic acid and cervicography (VIAC). The effectiveness of these methods can be increased if complemented by a human papillomavirus DNA detection tool since most cervical cancer cases are caused by persistent infection with high-risk human papillomavirus (HR-HPV) genotypes. Moreover, the possibility of multiple-genotype HR-HPV infections warrants the need for HPV detection tools with the capacity to detect both single and multiple infections. The aim of this study was to detect HR-HPV genotypes (HPV 16, 18, 31, 33, 35, 45, 51, 52, 56, and 58), using multiplex polymerase chain reaction (PCR), in stored cervicovaginal swabs from both HIV-positive and HIV-negative women reporting for routine cervical cancer screening. METHODOLOGY: Stored cervicovaginal swabs from sexually active women who underwent VIAC at the Parirenyatwa Referral Hospital in Harare, Zimbabwe, between February and April 2015 and had received HIV counselling and testing were genotyped for the selected 10 HR-HPV genotypes using in-house multiplex PCR. The results from the multiplex PCR were compared to those previously obtained when the same samples were HPV genotyped with next-generation sequencing (NGS) on an MiSeq platform (Illumina; USA). RESULTS: A total of 136 women were recruited and all 10 HR-HPV genotypes were detected. Quality control failed in 3 of the 136 swabs during the multiplex PCR reactions. The prevalence of HR-HPV genotypes in the study subjects was 53% (70/133). HIV-infected women were 1.67 times more likely to be infected with HR-HPV than were HIV-negative women (OR 1.67; p = 0.17). Of the 70 HR-HPV-positive cases, 37% (26/70) had multiple HR-HPV infections, and the majority of them were HIV infected. HIV-infected women were 1.86 times more likely to have multiple HR-HPV infections than HIV-negative women (OR 1.86; p = 0.20). Multiplex PCR and NGS had an almost perfect concordance rate in -HR-HPV detection (κ = 0.960), with only 3 discordant cases (negative with NGS and positive for HPV16 with multiplex PCR). CONCLUSION: Multiplex PCR can detect HR-HPV genotypes that are common in Zimbabwe and could be used to detect HR-HPV genotypes from women attending cervical cancer screening programs at the Parirenyatwa VIAC clinic in Harare.
Merkel Cell Polyomavirus Small T Antigen Induces DNA Damage Response.
Wu JH, Narayanan D, Limmer AL … +3 more , Simonette RA, Rady PL, Tyring SK
Intervirology · 2019 · PMID 31401636 · Publisher ↗
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin with high rates of metastasis and mortality. Besides well-established factors including genetic mutations and UV-induced DNA damage in Merkel...
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin with high rates of metastasis and mortality. Besides well-established factors including genetic mutations and UV-induced DNA damage in Merkel cell carcinogenesis, the recent discovery of the Merkel cell polyomavirus (MCPyV) has shed light on the viral etiology of MCC. In the current study, we provide novel evidence that MCPyV small T (sT) antigen induces the DNA damage response (DDR) pathway. Our data show that in human MCC cells, the presence of MCPyV is associated with hyperphosphorylation of histone H2AX, a marker for DNA damage. We observed that overexpression of MCPyV sT antigen induced the phosphorylation of histone H2AX as well as the activation of ataxia telangiectasia mutant (ATM), an upstream kinase important for H2AX phosphorylation. Moreover, we observed that MCPyV sT expression also induced the hyperphosphorylation of other ATM downstream molecules (including 53BP1 and CHK2) as well as the hypermethylation of histone 3 and histone 4. These findings disclose a novel link between MCPyV sT and the DDR pathway in MCC. Given that measurement of DDR is clinically useful for evaluating treatment response to radio- and chemotherapy, our findings warrant further investigation to evaluate the potential implications of this pathway for MCC management.
Altered Platelet Fatty Acids in Dengue Cases by Gas Chromatography-Mass Spectrometry Analysis.
Samadanam DM, Muthuraman KR, Mariappan V … +4 more , Kadhiravan T, Parameswaran N, Balakrishna Pillai AK, Rajendiran S
Intervirology · 2019 · PMID 31357191 · Publisher ↗
BACKGROUND: The role of dengue virus in altering the functional properties of platelets remains poorly understood. Few studies have observed that changes in fatty acids are found to have an effect on platelet activation...
BACKGROUND: The role of dengue virus in altering the functional properties of platelets remains poorly understood. Few studies have observed that changes in fatty acids are found to have an effect on platelet activation and aggregation. Also, platelet fatty acids have not been extensively studied in dengue so far. So, we aimed to study the fatty acids of platelet membranes in patients with dengue. METHODS: Gas chromatography-mass spectrometry (GC-MS) method was used to analyze fatty acids in the lipid extracts of platelets isolated from the study participants. RESULTS: GC-MS analysis of platelet lipids identified and quantified nearly 23 unique lipid molecules on platelet membrane. We observed significant alterations with some of the fatty acids in patients with dengue compared to controls. Within dengue cases, increase in unsaturated fatty acids in severe dengue was observed compared to non-severe dengue. From baseline to defervescence, no difference in fatty acids was observed in dengue platelets. This indicates that in dengue, platelet physiology remains altered even after the febrile phase. CONCLUSION: To the best of our knowledge, this is the first study characterizing the differential expression of platelet fatty acids in dengue infection. However, further studies are warranted to expound the underlying cause for thrombocytopenia and platelet dysfunction in dengue.
Efficient Human Cytomegalovirus Replication in Primary Endothelial Cells Is SOCS3 Dependent.
Sonzogni O, Millard AL, Taveira A … +5 more , Schneider MKJ, Duo L, Speck RF, Wulf GM, Mueller NJ
Intervirology · 2019 · PMID 31315128 · Publisher ↗
BACKGROUND: In immunocompromised patients, human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality. Suppressor of cytokine signaling (SOCS) proteins are very potent negative regulators of the j...
BACKGROUND: In immunocompromised patients, human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality. Suppressor of cytokine signaling (SOCS) proteins are very potent negative regulators of the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. We hypothesized that HCMV exploits SOCS1 and/or SOCS3 to its advantage. METHODS: All experiments were carried out with primary human lung-derived microvascular endothelial cells (HMVEC). SOCS1 and SOCS3 were silenced by transfecting the cells with siRNA. HCMV was propagated and titered on human lung-derived fibroblasts MRC5. Real-time PCR and Western blot were used to detect mRNA and protein levels, respectively. RESULTS: The data presented show that an efficient replication of HCMV in HMVEC is dependent on SOCS3 protein. Time course analysis revealed an increase in SOCS3 protein levels in infected cells. Silencing of SOCS3 (siSOCS3) resulted in inhibition of viral immediate early, early, and late antigen production. Consistently, HCMV titers produced by siSOCS3 cultures were significantly decreased when compared to control transfected cultures (siCNTRs). STAT1 and STAT2 phosphorylation was increased in siSOCS3-infected cells when compared to siCNTR-treated cells. CONCLUSION: These findings indicate the implication of SOCS3 in the mechanism of HCMV-mediated control of cellular immune responses.
HIV-1 Drug Resistance Mutations among Antiretroviral Drug-Experienced Patients in the South of Iran.
Memarnejadian A, Nikpoor AR, Davoodian N … +3 more , Kargar A, Mirzadeh Y, Gouklani H
Intervirology · 2019 · PMID 31311021 · Publisher ↗
BACKGROUND: The therapeutic effect of antiretroviral therapy (ART) is adversely influenced by antiretroviral drug resistance, mainly due to mutations (DRMs) in the human immunodeficiency virus (HIV) genome. These mutatio...
BACKGROUND: The therapeutic effect of antiretroviral therapy (ART) is adversely influenced by antiretroviral drug resistance, mainly due to mutations (DRMs) in the human immunodeficiency virus (HIV) genome. These mutations are commonly associated with HIV protease and reverse-transcriptase genes. We sought to determine the frequency of DRMs in a population of ART-experienced patients in the South of Iran. METHOD: A total of 44 HIV-1-positive participants under ART were selected from April 2016 to March 2017. Their DRMs, antiretroviral resistance status, and viral subtypes were determined. RESULTS: At least one DRM was detected in 61.4% of the participants. The highest frequency was related to nucleotide reverse-transcriptase inhibitor (NRTI) mutations (45.45%). In contrast, major protease inhibitor (PI) mutations had the lowest frequency (6.81%). M184V (40.9%) and K103N (25%), respectively related to NRTI and nonnucleoside reverse-transcriptase inhibitor (NNRTI), were the mutations with the highest frequencies. Susceptibility to PI drugs was higher compared to NRTIs and NNRTIs, which was consistent with the results of genotypic DRMs. CONCLUSION: The highest frequency of antiretroviral DRMs was related to NRTIs and NNRTIs. In contrast, PI resistance mutations had the lowest frequency. Laboratory-guided ART to avoid the expansion of mutants as well as investigating DRMs in other viral regions, such as integrase, are recommended.
The Use of Simple Laboratory Parameters in the Differential Diagnosis of Acute-Phase Zika and Dengue Viruses.
Musso D, Nhan TX, de Pina JJ … +2 more , Marchi J, Texier G
Intervirology · 2019 · PMID 31307046 · Publisher ↗
BACKGROUND: Differential diagnosis between acute-phase Zika and dengue is challenging because of a similar clinical presentation and the lack of available molecular diagnosis tools in most of endemic areas. OBJECTIVES: O...
BACKGROUND: Differential diagnosis between acute-phase Zika and dengue is challenging because of a similar clinical presentation and the lack of available molecular diagnosis tools in most of endemic areas. OBJECTIVES: Our study aimed to evaluate the use of simple laboratory parameters to differentiate these infections. METHODS: We retrospectively compared simple hematology and biochemistry values in 81 and 341 patients with confirmed Zika and dengue, respectively, collected from June 2013 to March 2014 during the French Polynesia outbreaks. RESULTS: Thrombocytopenia, neutropenia, leukopenia, lymphopenia, and elevated aspartate aminotransaminases were significantly more frequent in dengue than in Zika (p < 0.001). Platelets <100 × 109/L, neutrophils <0.5 × 109/L, lymphocytes <0.5 × 109/L, and aspartate aminotransaminases >100 IU/mL were found in dengue but not in Zika. The positive predictive value of the -association of leukocytes <4 × 109/L + lymphocytes <1 × 109/L + aspartate aminotransaminases >40 IU/mL for the diagnosis of dengue was 90%, with an accuracy of 82.4%. CONCLUSION: For the differential diagnosis between acute-phase Zika and dengue, there is no specific standard laboratory pattern. We identified cutoff values and a combination of laboratory parameters that are a strong argument against Zika and in favor of dengue.
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