Anti-HCV Monoclonal antibody, Clone OT6C-7[Biotin]

Background: Patients with chronic kidney failure and those undergoing chronic hemodialysis (CHD) treatment are at high risk of infection with hepatitis C virus (HCV). The incidence of occult HCV infection (OCI) in CHD remains controversial and the real burden of HCV in this population may be affected by the rate of OCI. This study evaluates the molecular assessment of OCI in CI-ID in an Iranian population. Methods: All subjects on CHD in the South Khorasan province of Iran were invited for participation in the study. Whole blood samples were taken and serological, clinical, and demographic information was recorded. HCV-RNAs were checked in serum and peripheral blood mononuclear cells (PBMCs) using an in-house semi-nested PCR assay. Viral load was determined using a real-time PCR-based quantification kit. Sequencing was performed to determine genotypes. Results: Overall, 120 cases participated in the study; 57.5% were male and the rest were female. In serum samples, no positive case was found for HCV-RNA. In PBMC samples, 2/120 (1.6%) were positive for HCV-RNA (95% CI, 0.002 to 0.059); the mean age of OCI positive cases was 37.5 +/- 19.2 years which was significantly lower than OCI negative cases (P = 0.026). Only one case had detectable viral load which was 49 IU/mL. The only HCV genotype identified was 1 a. Conclusion: This study showed that there is a risk of OCI among CHD patients; the very low and undetectable viral loads of OCI warrant further follow-up molecular testing for earlier diagnosis and treatment in the era of DAA.

Recent studies on chronic viral infections have defined a novel programmed cell death 1-positive (PD-1(+)) T cell factor 1-positive (TCF1(+)) stem-like CD8 T cell subset that gives rise to the terminally differentiated exhausted CD8 T cells. In this study, we performed T cell receptor beta (TCR beta) sequencing of virus-specific CD8 T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection to examine the TCR diversity and lineage relationship of these two functionally distinct subsets. We found that >95% of the TCR repertoire of the exhausted CD8 T cell subset was shared with the stem-like CD8 T cells. The TCR repertoires of both CD8 T cell subsets were composed mostly of a few dominant clonotypes, but there was slightly more breadth and diversity in the stemlike CD8 T cells than their exhausted counterpart (similar to 40 versus similar to 15 GP33(+) clonotypes; similar to 20 versus similar to 7 GP276(+) clonotypes). Interestingly, the breadth of the TCR repertoire was broader during the early stages (day 8) of the chronic infection than the later stages (days 45 to 60), showing that there was a narrowing of the TCR repertoire during chronic infection (similar to 2-fold GP33(+) and GP276(+) stem-like subset; similar to 10-fold GP33(+) and similar to 5-fold GP276(+) exhausted subset). In contrast, during acute LCMV infection, the TCR repertoire was much broader in both GP33-specific effector (similar to 160 clonotypes) and memory CD8 T cells (similar to 160 clonotypes). Overall, our data demonstrate that the virus-specific CD8 T cell TCR repertoire is broad and remains stable after acute LCMV infection, but it contracts and is narrower during chronic infection. Our study also shows that the repertoire of the exhausted CD8 T cell subset is almost completely derived from the stem-like CD8 T cell subset during established chronic LCMV infection. IMPORTANCE CD8 TCR repertoires responding to chronic viral infections (HIV, hepatitis C virus [HCV], Epstein-Barr virus [EBV], and cytomegalovirus [CMV]) have limited breadth and diversity. How these repertoires change and are maintained throughout the chronic infection are unknown. We thus characterized the LCMV-specific CD8 TCR repertoires of stem-like and terminally exhausted subsets generated during chronic LCMV infections. During chronic LCMV infections, the repertoires started as diverse but became more clonal at the late time point. Further, the exhausted subset was composed of dominant clonotypes that were shared with the stem-like subset. Together, we demonstrate that the TCR repertoire contracts over time and is almost exclusively derived from the stem-like subset late during the persistent viral infection. Our data suggest that dominant clonotypes in the exhausted subset are derived from a diverse pool of stem-like clonotypes, which may be contributing to the clonality observed during chronic viral infections.