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Background: The hepatitis B e antigen (HBeAg)‐negative infection Phase 3 is characterized by no or minimal signs of hepatic inflammation and the absence of hepatic fibrosis. However, underlying molecular mechanisms leading to this benign phenotype are poorly understood. Methods: Genotype A, B and D HBeAg‐negative patient isolates with precore mutation G1896A from Phase 3 were analysed in comparison with respective HBeAg‐positive rescue mutant and HBeAg‐positive wild‐type reference genomes regarding differences in viral replication, morphogenesis, infectivity and impact on NF‐E2‐related factor 2 (Nrf2)/antioxidant response element (ARE)‐dependent gene expression and cellular kinome. Results: In comparison with reference genomes, the patient isolates are characterized by a lower intra‐ and extracellular hepatitis B surface antigen (HBsAg)‐amount, and HBsAg‐retention in the endoplasmic reticulum. Rescue of HBeAg expression increased HBsAg‐amount but not its release. Expression of the isolated genomes is associated with a higher Nrf2/ARE‐dependent gene expression as compared to reference genomes independent of HBeAg expression. Kinome analyses revealed a decreased activity of receptors involved in regulation of proliferative pathways for all patient isolates compared to the reference genomes. No specific conserved mutations could be found between all genomes from Phase 3. Conclusions: HBeAg‐negative genomes from Phase 3 exhibit distinct molecular characteristics leading to lower HBsAg synthesis and release, enhanced oxidative stress protection and decreased activity of key kinases, triggering an antiproliferative stage, which might contribute to the lower probability of hepatocellular carcinoma. The observed differences cannot be associated with loss of HBeAg or specific mutations common to all analysed isolates, indicating the phenotype of Phase 3 derived genomes to be the result of a multifactorial process likely reflecting a conserved natural selection process. [ABSTRACT FROM AUTHOR]

BACKGROUND: The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we aimed to investigate the phylogenetic characteristics of SARS-CoV-2 infections in Chicago, Illinois, and assess their relationship to clinical parameters. METHODS: We performed whole-genome sequencing of SARS-CoV-2 isolates collected from COVID-19 patients in Chicago in mid-March, 2020. Using these and other publicly available sequences, we performed phylogenetic, phylogeographic, and phylodynamic analyses. Patient data was assessed for correlations between demographic or clinical characteristics and virologic features. FINDINGS: The 88 SARS-CoV-2 genome sequences in our study separated into three distinct phylogenetic clades. Clades 1 and 3 were most closely related to viral sequences from New York and Washington state, respectively, with relatively broad distributions across the US. Clade 2 was primarily found in the Chicago area with limited distribution elsewhere. At the time of diagnosis, patients infected with Clade 1 viruses had significantly higher average viral loads in their upper airways relative to patients infected with Clade 2 viruses, independent of disease severity. INTERPRETATION: These results show that multiple variants of SARS-CoV-2 were circulating in the Chicago area in mid-March 2020 that differed in their relative viral loads in patient upper airways. These data suggest that differences in virus genotype can impact viral load and may influence viral spread. FUNDING: Dixon Family Translational Research Award, Northwestern University Clinical and Translational Sciences Institute (NUCATS), National Institute of Allergy and Infectious Diseases (NIAID), Lurie Comprehensive Cancer Center, Northwestern University Emerging and Re-emerging Pathogens Program.

Background: Human polyomaviruses (HPyVs) have been associated with several cutaneous inflammatory conditions. More investigation is needed to identify further presentations of cutaneous pathology associated with HPyVs. Our aim was to investigate the possible association of skin-tropic HPyVs with folliculitis, particularly eosinophilic pustular folliculitis (EPF).Methods: This study included 55 Japanese patients, comprising 13 patients with EPF and 42 patients with suppurative folliculitis. HPyV DNAs were detected by quantitative polymerase chain reaction. Expression of viral antigen and geographically related viral genotypes were also assessed.Results: Human polyomavirus 6 (HPyV6) DNA was found in 9 of 13 (69%) patients with EPF, a rate significantly higher than that found in suppurative folliculitis (1/42; 2%). Of the 7 HPyV6 DNA-positive EPF specimens analyzed, 4 were positive for HPyV6 small tumor antigen. All the HPyV6 strains detected in this study were of the Asian/Japanese genotype.Conclusions: The predominant detection of HPyV6 DNA and the expression of viral antigen suggest a possible association between HPyV6 infection and EPF in a subset of patients. Worldwide studies are warranted to determine whether Asian/Japanese genotype HPyV6 is associated preferentially with the incidence and pathogenesis of this eosinophil-related skin disease that has an ethnic predilection for the East Asian population. [ABSTRACT FROM AUTHOR]

Background: The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we aimed to investigate the phylogenetic characteristics of SARS-CoV-2 infections in Chicago, Illinois, and assess their relationship to clinical parameters. Methods: We performed whole-genome sequencing of SARS-CoV-2 isolates collected from COVID-19 patients in Chicago in mid-March, 2020. Using these and other publicly available sequences, we performed phylogenetic, phylogeographic, and phylodynamic analyses. Patient data was assessed for correlations between demographic or clinical characteristics and virologic features. Findings: The 88 SARS-CoV-2 genome sequences in our study separated into three distinct phylogenetic clades. Clades 1 and 3 were most closely related to viral sequences from New York and Washington state, respectively, with relatively broad distributions across the US. Clade 2 was primarily found in the Chicago area with limited distribution elsewhere. At the time of diagnosis, patients infected with Clade 1 viruses had significantly higher average viral loads in their upper airways relative to patients infected with Clade 2 viruses, independent of disease severity. Interpretation: These results show that multiple variants of SARS-CoV-2 were circulating in the Chicago area in mid-March 2020 that differed in their relative viral loads in patient upper airways. These data suggest that differences in virus genotype can impact viral load and may influence viral spread. Funding: Dixon Family Translational Research Award, Northwestern University Clinical and Translational Sciences Institute (NUCATS), National Institute of Allergy and Infectious Diseases (NIAID), Lurie Comprehensive Cancer Center, Northwestern University Emerging and Re-emerging Pathogens Program.

Background: In hepatitis C virus (HCV), infection viral and IL28B genotype along with many clinical and biochemical factors can influence response rates to pegylated interferon plus ribavirin (Peg-IFN-a/R) therapy and progression to chronic hepatitis C (CHC). Aims: The present study was conducted to determine the effect of biochemical and risk factors on treatment outcome in CHC patients in relation to their viral and host genotype. Settings and Design: The present study was a prospective Pe- IFN efficacy study consisting of Peg-IFN-a/R therapy for 24–48 weeks including 250 HCV infected patients. Materials and Methods: Biochemical parameters were determined by Beckman Coulter AU680 automated analyzer. HCV and Interleukin 28B (IL28B) genotyping were carried out by polymerase chain reaction-restriction fragment length polymorphism and viral load was determined by quantitative real-time PCR. Results: Wild outnumbered the variant genotypes in rs 12979860, rs 12980275, and rs 8099917 SNP of IL28B gene. Sustained virological response (SVR) SVR and viral genotype were significantly associated with age, hepatic steatosis, low-grade varices, and serum aspartate transaminase levels (at the end of treatment) (P < 0.05). In addition, SVR was significantly influenced by body mass index (BMI), insulin resistance, serum low-density lipoprotein , and ferritin levels (P < 0.05). Viral genotype 1 infected patients had higher serum cholesterol and triglyceride levels (P < 0.05). Conclusions: Although the IL28B sequence variation is the major factor that can influence response rates to antiviral therapy, viral and biochemical factors also have a definite role to play in the diagnosis, etiology, and treatment outcome in HCV-infected patients.

Background: Human skin microorganisms have been associated with various skin diseases. However, most studies have focused on bacterial communities, and little is known about normally resident skin viruses such as the Polyomaviridae and their association with cutaneous disorders.Methods: We investigated the infection levels of Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), and human polyomavirus 7 (HPyV7), using triplet skin swabs collected from lesional and nonlesional skins of 86 Japanese patients with inflammatory skin diseases and mycosis fungoides, and from 149 healthy control individuals.Results: This age-matched case-control study provides the first analyses of the loads of polyomaviruses in association with various skin diseases. The viral loads were significantly higher for HPyV6/HPyV7 and lower for MCPyV in patients with psoriasis. The viral load variation was observed not only at lesion sites, but also at clinically unaffected skin sites in most of the patients. The viral strains tested were all of the Asian/Japanese genotype.Conclusions: Our findings suggest a covariation in the infection levels of cutaneous polyomaviruses in certain inflammatory skin conditions. Worldwide prospective longitudinal studies are warranted to understand the influence of such alterations on the pathogenesis of inflammatory skin disorders. [ABSTRACT FROM AUTHOR]

Children and adults residing in densely populated urban centers around the world are at risk of seasonal influenza-like illness caused by respiratory viruses such as influenza virus, human metapneumovirus (hMPV), and respiratory syncytial virus (RSV). In a large metropolitan of Thailand's capital city Bangkok, most respiratory infections are rarely confirmed by molecular diagnostics. We therefore examined the frequency of RSV, hMPV, and influenza virus in 8,842 patients who presented influenza-like illness and sought medical care at a large hospital in Bangkok between 2016 and 2017. Using a multiplex real-time reverse-transcription polymerase chain reaction (RT-PCR), 30.5% (2,699/8,842) of nasopharyngeal (NP) swab samples tested positive for one or more of these viruses. Influenza virus comprised 17.3% (1,528/8,842), of which the majority were influenza A/H3N2. Such infection was most prevalent among adults and the elderly. RSV was identified in 11.4% (1,011/8,842) and were mostly ON1 and BA9 genotypes. Of the hMPV-positive samples (3.6%, 318/8,842), genotypes A2, B1, and B2 were detected. A small number of individuals experienced co-infections (1.8%, 155/8,842), most commonly between RSV and influenza A/H3N2. RSV and hMPV co-infections were also found, but mainly in young children. Viral respiratory tract infection peaked locally in the rainy season (June to September). These findings support the utility of rapid nucleic acid testing of RSV, hMPV, and influenza virus in patients with ILI. [ABSTRACT FROM AUTHOR]

Hepatitis C is a serious problem for Russian Federation. Determination of HCV genotype/subtype is needed for epidemic control, development of antiviral drugs, vaccines, and planning expenditures for treatment. The aims of the study were to establish the structure of HCV genotype in infected children in Moscow region and to analyse the features of hepatitis, induced by different viral subtypes. Methods. HCV RNA was detected by RT-PCA with a high sensitivity (15 ME/ml). Viral genotyping and determination of intergenotype recombination were done by sequencing HCV genome regions of 5'-NTR-core and NS5B. HCV nucleocapsid antigen (core-Ag) revealing and quantifing in serum were done by ELISA and immunochemioluminesent method. Antibodies to individual structural and nonstructural HCV antigens were determined by ELISA. The level of specific antibodies was determined by titration. Routes of HCV transmission was established by a survey by of parents using the standard protocol. Results. The average age of 63 infected children was 11.3 ± 0.78 years. The main HCV subtypes were 3a (46.03%), 1b (33.3%), and 1a (11.6%). Three children (4.8%) showed intergenotype recombinant RF_2k/1b. Most children have been infected by vertical transmission (69.8%). In order to identify significant differences in hepatitis features we analyzed three groups of children with chronic hepatitis C: the first group - 10 children with subtype 3a, the second group - 10 patients with subtype 1b, and the third group - 7 participants with subtype 1a. There are no significant differences in the symptoms, syndromes and biochemical parameters in these groups. The value of viral load and core-Ag were significantly higher in patients with subtype 3a (P < 0.1) than in the groups of children infected with subtype 1a or 1b. Anti-HCV IgM, anti-NS4 IgG and anti-NS5 IgG in patients, chronically infected by subtype 3a, were detected less often (p < 0.05) than in the other groups. conclusion. The proportion of HCV subtype 3a has increased in infected children in the Moscow region. Intergenotype recombinant RF_2k/1b was firstly detected in children. Patients, infected by HCV subtype 3a, displayed higher viral load and often lack of anti-HCV IgM, anti-NS4ab IgG, and anti-NS5a IgG. Children, infected by HCV subtypes 1a, 1b, and 3a, have no significant differences in the symptoms, syndromes and liver biochemical parameters.

Introduction: Viral genotype and variation in host genes involved in the immune response may predict the treatment response in patients infected with HCV. The present study was designed to determine the distribution pattern of HCV and host genotypes in Chronic Hepatitis C (CHC) patients and their association with virological response and other risk factors. Methodology: Two hundred and fifty (n = 250) HCV positive patients were included in the study. HCV and Interleukin 28B (IL28B) genotyping was carried out by PCR-RFLP. Results: Viral genotype 3 was the predominant genotype seen in 187 (74.8%) patients. Wild genotype predominated in rs12979860, rs12980275 and rs8099917 SNP of IL28B gene. A significant difference was found in end stage virological response (EVR) between HCV genotype 1 infected patients with wild and variant genotype for rs12980275 and rs8099917 SNPs respectively (P < 0.05). On multivariate analysis all the SNPs were found to be associated with each other (P < 0.05) with rs12980275 SNP associated with history of Jaundice (P < 0.05). Viral genotype 3 was significantly associated with age (< 50 years) and rapid virological response (RVR) while as viral genotype 1 was significantly associated with history of surgery on multivariate analysis (P < 0.05). Conclusions: The viral genotype and IL28B polymorphisms are important factors to personalize antiviral therapy of patients with CHC. [ABSTRACT FROM AUTHOR]

We have developed a dynamic epidemiological model informed by records of viral presence and genotypes to evaluate potential transmission routes maintaining a viral pathogen in economically and culturally important anadromous fish populations. In the Columbia River Basin, infectious hematopoietic necrosis virus (IHNV) causes severe disease, predominantly in juvenile steelhead trout ( Oncorhynchus mykiss ) and less frequently in Chinook salmon ( O. tshawytscha ). Mortality events following IHNV infection can be devastating for individual hatchery programs. Despite reports of high local mortality and extensive surveillance efforts, there are questions about how viral transmission is maintained. Modeling this system offers important insights into disease transmission in natural aquatic systems, as well as about the data requirements for generating accurate estimates about transmission routes and infection probabilities. We simulated six scenarios in which testing rates and the relative importance of different transmission routes varied. The simulations demonstrated that the model accurately identified routes of transmission and inferred infection probabilities accurately when there was testing of all cohort-sites. When testing records were incomplete, the model accurately inferred which transmission routes exposed particular cohort-sites but generated biased infection probabilities given exposure. After validating the model and generating guidelines for result interpretation, we applied the model to data from 14 annual cohorts (2000–2013) at 24 focal sites in a sub-region of the Columbia River Basin, the lower Columbia River (LCR), to quantify the relative importance of potential transmission routes in this focal sub-region. We demonstrate that exposure to IHNV via the return migration of adult fish is an important route for maintaining IHNV in the LCR sub-region, and the probability of infection following this exposure was relatively high at 0.16. Although only 1% of cohort-sites experienced self-exposure by infected juvenile fish, this transmission route had the greatest probability of infection (0.22). Increased testing and/or determining whether transmission can occur from cohort-sites without testing records (e.g., determining there was no testing record because there were no fish at the cohort-site) are expected to improve inference about infection probabilities. Increased use of secure water supplies and continued use of biosecurity protocols may reduce IHNV transmission from adult fish and juvenile fish within the site, respectively, to juvenile salmonids at hatcheries. Models and conclusions from this study are potentially relevant to understanding the relative importance of transmission routes for other important aquatic pathogens in salmonids, including the agents of bacterial kidney disease and coldwater disease, and the basic approach may be useful for other pathogens and hosts in other geographic regions. [ABSTRACT FROM AUTHOR]

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Background: In hepatitis C virus (HCV), infection viral and IL28B genotype along with many clinical and biochemical factors can influence response rates to pegylated interferon plus ribavirin (Peg-IFN-a/R) therapy and progression to chronic hepatitis C (CHC). Aims: The present study was conducted to determine the effect of biochemical and risk factors on treatment outcome in CHC patients in relation to their viral and host genotype. Settings and Design: The present study was a prospective Pe- IFN efficacy study consisting of Peg-IFN-a/R therapy for 24–48 weeks including 250 HCV infected patients. Materials and Methods: Biochemical parameters were determined by Beckman Coulter AU680 automated analyzer. HCV and Interleukin 28B (IL28B) genotyping were carried out by polymerase chain reaction-restriction fragment length polymorphism and viral load was determined by quantitative real-time PCR. Results: Wild outnumbered the variant genotypes in rs 12979860, rs 12980275, and rs 8099917 SNP of IL28B gene. Sustained virological response (SVR) SVR and viral genotype were significantly associated with age, hepatic steatosis, low-grade varices, and serum aspartate transaminase levels (at the end of treatment) (P < 0.05). In addition, SVR was significantly influenced by body mass index (BMI), insulin resistance, serum low-density lipoprotein , and ferritin levels (P < 0.05). Viral genotype 1 infected patients had higher serum cholesterol and triglyceride levels (P < 0.05). Conclusions: Although the IL28B sequence variation is the major factor that can influence response rates to antiviral therapy, viral and biochemical factors also have a definite role to play in the diagnosis, etiology, and treatment outcome in HCV-infected patients. [ABSTRACT FROM AUTHOR]

Objectives: Because torque teno virus (TTV) has been implicated in tumorigenesis as a cocarcinogen, we studied TTV prevalence in saliva and biopsy samples from head and neck cancer (HNCC) patients, patients with premalignant lesions of oral cancer, and controls. We also wished to determine the TTV genotypes in HNCC patients. Methods: A seminested polymerase chain reaction (PCR) amplifying the N22 region of the TTV genome, as well as direct sequencing of PCR fragments, was used. Results: TTV prevalence was higher in HNCC patients (saliva: 27/71, 38%; tumor biopsy: 22/74, 30%) than in controls (saliva: 8/56, 14%; oral mucosa: 1/19, 5%). TTV prevalence was also high in patients with premalignant lesions of oral carcinoma (saliva: 9/18, 50%; biopsy: 5/21, 24%). By phylogenetic analysis, TTV belonging mostly to genotypes 1 and 2 was found in HNCC patients. In most of the cases, identical TTV strains were present in the biopsy and salivary sample of the same HNCC patient. In addition, the same TTV strain was detected in 2 laryngeal carcinoma biopsies obtained from 2 independent patients. Conclusions: Our data are compatible with the idea that TTV might act as a cocarcinogen in certain cases of HNCC. Alternatively, HNCC may facilitate either TTV replication or TTV entry into the saliva. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus infection is a leading cause for chronic liver disease. It has wide population specific genotype variability. Genotype knowledge and viral load assessment are equally important for designing therapeutic strategies and as predictors of treatment outcome among hepatitis C (HCV) infected patients. Materials and Methods: Between June 2012 and 2013 an observational study was conducted among 350 chronic hepatitis patients visiting Calcutta National Medical College, Kolkata, India. Among them, 110 anti-HCV antibody positive cases were diagnosed and subjected to viral RNA extraction, viral genotyping and viral load quantification using polymerase chain reaction (PCR) based techniques. Statistical Analysis: Statistical analysis was done with IBM SPSS Statistics software, version 20. p-value

The present study aimed to evaluate the molecular epidemiology of HBV in chronic HBV infected cases from northeast India (NEI), since scanty data are available from the region which has a predominant ethnically distinct tribal population. A total of 523 clinically diagnosed index chronic HBV infected cases and 172 asymptomatic patients (based on family screening) were enrolled with informed consent. Patients were stratified based on serology, imaging, pathology, and clinical data and grouped as chronic HBV and cirrhotic cohorts. Analysis for serum HBV DNA levels and HBV genotyping was performed, and was statistically co-related with disease severity. Males were more prone to chronic HBV infection. Majority of the patients who had Chronic HBV infection based on family screening were females (59.88%), majorly wives of index patients. Mean viral load in Chronic HBV patients was almost 4.5-folds higher than cirrhosis patients, and was significantly associated with e-antigen positive status( P < 0.001) in both groups. HBV genotype D was the most prevalent genotype (62.30%) in NEI. Mixed genotype infection of A + D was found from Assam, along with C + D cases (1.29%) cumulatively. There is a high prevalence of HBV genotype C (13.96%) in our studied cohort which was found to be associated with higher viral load( P = 0.018), e-antigen positivity( P = 0.043), and increased cirrhosis risk compared to Chronic HBV cases [OR = 1.670]. Family contacts in NEI are prone to infection with HBV and development of Chronic HBV. Higher presence of e-positive cases and genotype C along with the mixed genotypes in NEI is unique and of significance with reference to predisposition to disease severity and even response to antiviral therapy. J. Med. Virol. 87:1539-1548, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Highlights: [•] We applied various methods to reveal positive selection signals in HBV genome. [•] Positively selected codons are associated with disease stages and viral genotypes. [•] Immune surveillance, anti-viral treatment, and viral replication fitness are driving forces of HBV adaptive evolution. [•] Selections at nucleotide level are also identified to be associated with disease stage. [•] A few mutations are under the process of fixation in viral adaptive evolution. [ABSTRACT FROM AUTHOR]

SUMMARY Esophageal squamous cell carcinoma (ESCC) is one of the common cancers with a poor prognosis. Incidences of human papillomavirus (HPV) infection range from 0 to 67% in different parts of the world. It has been frequently associated with high-risk HPV genotypes 16 and 18. The present study analyzes the prevalence of HPV infection in ESCC tumor and adjoining mucosa. Fresh tissue samples were obtained from ESCC tumor (group I) and adjoining mucosa (group II). Aliquots of DNA extracts were used. There were 23 patients with paired samples, 19 (83%) were male. HPV was positive in 20/23 (87%). Mean age of HPV positive in group I was 56.63 ± 6.96 and in group II 54.31 ± 7.13 years ( P > 0.05). Majority had more than one viral type. HPV52 was the most common observed in 14 (61%) males and two (9%) females. Other common viruses were HPV55, 39, and 59. Smoking had a significant association with viral positivity. p63 and p16 oncoproteins correlated with degree of tumor differentiation but not with viral status. We documented high prevalence of high-risk HPV in ESCC. Our observations support the concept of persistent infection by an oncogenic HPV in cancer development. Our study highlights importance of documenting viral genotype in a defined geographic area. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B virus patients are usually treated in Syria with alpha interferon and nucleos(t)ide analogues. Genotypic viral factors causing inadequate response or relapse following initial response are not routinely investigated. This study aimed to explore and discuss local therapeutic decisions from a molecular perspective. Methodology: Fifty patients with hepatitis B from Syria were tested for HBV genotyping and drug-resistance mutations by DNA sequencing. Results: All patients had genotype D, which is characterized by relatively low response to interferon-based therapy. Drug-resistant viral mutant variants were detected in one fifth of the enrolled patients, and distributed similarly in both nucleos(t)ide analogues-naïve and -treated patients. However, nucleos(t)ide analogues-based therapy was associated with the existence of more mutations and hence increased resistance. Conclusions: Investigating HBV genotypes and drug-resistance mutations to support treatment decisions is critically needed for efficient therapy and patients' survival. [ABSTRACT FROM AUTHOR]

Objective: This work investigated the profile of inflammation biomarkers in patients with chronic hepatitis C and its association with liver fibrosis, hepatic necroinflammatory activity, viral genotypes and cryoglobulinemia. Subjects and methods: Seventy-eight untreated patients were studied. Biomarker levels were determined by immunoassays, cryoglobulinemia by cryoprecipitation and liver histopathology investigated using METAVIR scores. Results: Decreased levels of α-acid glycoprotein (AGP), C3 and haptoglobin (Hp) were observed in the patients ( P < 0.0001). Increased α-antitrypsin ( P < 0.01) and ferritin ( P < 0.0001) levels were found in this group, but C-reactive protein (CRP) and C4 levels were unaltered. Alanine aminotransferase inversely correlated with Hp ( P < 0.01) and AGP ( P = 0.01), whereas it was directly correlated with ferritin ( P < 0.05) and AGP ( P < 0.0001). The levels of CRP, C3 and C4 were lower in the patients with hepatic necroinflammatory activity ( P < 0.05). Patients with advanced fibrosis had low levels of Hp and AGP ( P < 0.05 and P < 0.01, respectively). Neither infection with different viral genotypes nor cryoglobulinemia caused an alteration in biomarker levels. Conclusion: Chronic hepatitis C virus infection alters the levels of some biomarkers, which are mainly observed in patients with liver fibrosis and hepatic necroinflammatory activity. [ABSTRACT FROM AUTHOR]

Sugarcane yellow leaf virus (SCYLV) (genus Polerovirus, family Luteoviridae), the causal agent of sugarcane yellow leaf disease (YLD), was first detected in China in 2006. To assess the distribution of SCYLV in the major sugarcane-growing Chinese provinces, leaf samples from 22 sugarcane clones ( Saccharum spp. hybrid) showing YLD symptoms were collected and analyzed for infection by the virus using reverse transcription PCR (RT-PCR), quantitative RT-PCR, and immunological assays. A complete genomic sequence (5,879 nt) of the Chinese SCYLV isolate CHN-FJ1 and partial genomic sequences (2,915 nt) of 13 other Chinese SCYLV isolates from this study were amplified, cloned, and sequenced. The genomic sequence of the CHN-FJ1 isolate was found to share a high identity (98.4-99.1 %) with those of the Brazilian (BRA) genotype isolates and a low identity (86.5-86.9 %) with those of the CHN1 and Cuban (CUB) genotype isolates. The genetic diversity of these 14 Chinese SCYLV isolates was assessed along with that of 29 SCYLV isolates of worldwide origin reported in the GenBank database, based on the full or partial genomic sequence. Phylogenetic analysis demonstrated that all the 14 Chinese SCYLV isolates clustered into one large group with the BRA genotype and 12 other reported SCYLV isolates. In addition, five reported Chinese SCYLV isolates were grouped with the Peruvian (PER), CHN1 and CUB genotypes. We therefore speculated that at least four SCYLV genotypes, BRA, PER, CHN1, and CUB, are associated with YLD in China. Interestingly, a 39-nt deletion was detected in the sequence of the CHN-GD3 isolate, in the middle of the ORF1 region adjacent to the overlap between ORF1 and ORF2. This location is known to be one of the recombination breakpoints in the Luteoviridae family. [ABSTRACT FROM AUTHOR]

Abstract: Dengue is an expanding arboviral disease of variable severity characterized by the emergence of virus strains with greater fitness, epidemic potential and possibly virulence. To investigate the role of dengue virus (DENV) strain variation on epidemic activity we studied DENV-2 viruses from a series of South Pacific islands experiencing outbreaks of varying intensity and clinical severity. Initially appearing in 1971 in Tahiti and Fiji, the virus was responsible for subsequent epidemics in American Samoa, New Caledonia and Niue Island in 1972, reaching Tonga in 1973 where there was near-silent transmission for over a year. Based on whole-genome sequencing and phylogenetic analysis on 20 virus isolates, Tonga viruses were genetically unique, clustering in a single clade. Substitutions in the pre-membrane (prM) and nonstructural genes NS2A and NS4A correlated with the attenuation of the Tongan viruses and suggest that genetic change may play a significant role in dengue epidemic severity. [ABSTRACT FROM AUTHOR]

Background & Aims: Little is known about the level of hepatitis B virus (HBV) DNA in individuals with chronic, inactive HBV infections. Patients who test positive for the antibody to hepatitis B e antigen (anti-HBe) and have normal levels of alanine aminotransferase for more than 10 years have a low risk of HBV reactivation and are considered to be inactive carriers. We investigated HBV DNA levels in inactive carriers and identified factors that correlated with this state among anti-HBe–positive carriers with HBV DNA levels of 104 copies/mL or greater (5.26 copies/mL = 1 IU/mL). Methods: HBV DNA levels were assayed in 250 inactive carriers with persistently normal alanine aminotransferase levels for more than 10 years. Clinical and virologic features were compared between inactive carriers (with HBV DNA levels ≥104 copies/mL) and age-matched patients with HBe antigen–negative chronic hepatitis (controls, n = 90). Results: The median level of HBV DNA among inactive carriers was 3.70 log10 copies/mL (range, undetectable to 5.98 log10 copies/mL). Ninety (36%) had levels of 104 copies/mL or greater. Compared with control patients, significant differences of inactive carriers included sex (more female patients), lower HBV DNA levels, and lower prevalence of genotype C virus and the basal core promoter mutation T1762/A1764. The prevalence of the precore mutation A1896 was similar between groups. Multiple logistic regression analyses identified male sex, HBV DNA levels greater than 105 copies/mL, and the basal core promoter mutation as independent factors that correlated with active disease. Conclusions: Nearly 40% of inactive carriers had HBV DNA levels of 104 copies/mL or greater. Female sex, HBV DNA levels of 104 to 105 copies/mL, and wild-type basal core promoter correlated with inactive carrier state. [Copyright &y& Elsevier]

Abstract: Background: Increasing data shows the relevance of HBV genotypes in the outcome of infection. Most studies investigating the relationship between the genotypic characteristics of hepatitis B virus (HBV) and the clinical or epidemiological aspects of HBV infection originate from studies of patients with chronic rather than acute hepatitis B. Objectives: To study a convenience sample representing ca. 5% of reported acute hepatitis B in England between 1997 and 2001 to investigate the distribution of HBV genotypes and specific HBV variants with epidemiological risk factors, thereby providing baseline data for ongoing surveillance. Study design: From 160 serum samples, PCR was carried out to amplify the first 600 bases of the HBV S gene. Amplicons were sequenced and subjected to phylogenetic analysis and risk factor analysis. Results: Fifty-seven percent of the study samples carried HBV belonging to subtype A2, 13% to subtype D2, and the rest to genotype E (8%) and subtypes C2 and D3 (each 6%), D1 and D4 (each 3%) and B4 (1%). One particular A2 isolate was dominant, accounting for 23% of the total sample set. Drug use and homosexual transmission were equally implicated as risks within genotype A2. No mutations associated with vaccine escape or resistance to antiviral therapy were identified. Conclusion: Immigration and travel likely shape the observed genotype distribution and consequent prevalence of genotypes other than A2 or D in this population. Data suggests no genetic separation of parenteral and sexually transmitted virus. These data demonstrate the value in pursuing more extensive and recent surveillance. [Copyright &y& Elsevier]

Background: The ethnic influence makes it difficult to reach a consensual definition of host-dependent genetic factors controlling the hepatitis C virus (HCV) disease course. Aims: To investigate, in an ethnically complex Brazilian population, whether human leucocyte antigen (HLA) molecules are associated with susceptibility to HCV infection, self-limiting viral clearance and predisposition to chronic disease. Methods: One hundred and four HCV-antibody-positive patients (stratified into groups with spontaneous viral clearance and chronic HCV infection) and 166 healthy controls were submitted to HLA genotyping. Results: Two strong associations were observed between the susceptibility to HCV infection and DRB3 [odds ratio (OR), 4.03; 95% confidence interval (CI), 2.40–6.77; Pc=0.0000041] and DQB1* 02 (OR, 1.72; 95% CI, 1.05–2.84; P=0.041), and between the spontaneous viral clearance and DRB1* 01 (OR, 4.59; 95% CI, 1.70–12.41; P=0.003) and DQB1* 03 (OR, 2.83; 95% CI, 1.14–7.02; P=0.029). No evidence was observed regarding the epidemiology or viral genotype influence on the disease course. Conclusion: We could confirm with a highly admixed population the association of viral clearance with two allele groups ( DRB1* 01 and DQB1* 03) previously reported in homogeneous populations. The identification of DRB1* 01 and DQB1* 03 involved with self-limiting hepatitis in different ethnic groups is a very important finding that will contribute to the current knowledge about HCV–host interaction and the development of therapeutic vaccines. [ABSTRACT FROM AUTHOR]

Interferon (IFN)-α plus ribavirin is an effective treatment for hepatitis C virus (HCV) infection, but is associated with a high rate of depression. Depression has been linked to a worse outcome in multiple medical disorders including viral illnesses. We examined whether increased symptoms of depression during IFN-α/ribavirin therapy were associated with a reduced treatment response as assessed by clearance of HCV. Depressive symptoms were evaluated in 102 HCV-infected patients at baseline and after 4, 8, 12, and 24 weeks of pegylated IFN-α-2b plus ribavirin therapy using the Zung self-rating depression scale (SDS). Viral clearance was determined at 24 weeks by polymerase chain reaction (PCR). Only 34% of subjects (10 out of 29) with a 20-point or greater increase in SDS Index score were HCV PCR negative at 24 weeks, compared to 59% (24 out of 41) of patients with a 10–19 point increase in SDS Index and 69% (22 out of 32) of patients with a less than 10 point increase (χ2=7.6, df=2, p<0.05). In addition, a 20-point or greater increase in SDS Index score during IFN-α/ribavirin therapy significantly predicted failure to clear virus when considered alone [crude odds ratio (OR), 3.2; 95% confidence interval (CI), 1.3–8.0; p<0.01] or when controlling for other factors that affected IFN-α treatment response (adjusted OR, 3.6; 95% CI, 1.3–9.5; p=0.01). These preliminary findings suggest that individuals who experience significant increases in depressive symptoms during IFN-α/ribavirin therapy may be less likely to clear virus, highlighting the importance of identifying and treating depressive symptoms in this patient population. [Copyright &y& Elsevier]

Background: Hepatitis C virus infection is a leading cause for chronic liver disease. It has wide population specific genotype variability. Genotype knowledge and viral load assessment are equally important for designing therapeutic strategies and as predictors of treatment outcome among hepatitis C (HCV) infected patients. Materials and Methods: Between June 2012 and 2013 an observational study was conducted among 350 chronic hepatitis patients visiting Calcutta National Medical College, Kolkata, India. Among them, 110 anti-HCV antibody positive cases were diagnosed and subjected to viral RNA extraction, viral genotyping and viral load quantification using polymerase chain reaction (PCR) based techniques. Statistical Analysis: Statistical analysis was done with IBM SPSS Statistics software, version 20. p-value <0.05 was regarded as statically significant. Results: Among 66 HCV RNA positive cases, genotypes 1a, 3a and 3b were observed among 18 (27%), 44(67%) and 4(6%) cases respectively. Genotype 3a had higher viral load than patients infected with genotypes 1 and 3b. However, no statistical significance was observed for viral load among the various HCV RNA genotypes. Conclusion: Genotype 3a accounted for the highest number of cases with positive HCV RNA. However, no statistically significant difference existed for viral load among the various HCV RNA genotypes in this study. [ABSTRACT FROM AUTHOR]