Abstract
The hepatitis B virus (HBV) and the human immunodeficiency virus type 1 (HIV-1) can infect cells of the lymphatic system. It is unknown whether HIV-1 co-infection impacts infection of peripheral blood mononuclear cell (PBMC) subsets by the HBV. Aims To compare the detection of HBV genomes and HBV sequences in unsorted PBMCs and subsets (i.e., CD4+ T, CD8+ T, CD14+ monocytes, CD19+ B, CD56+ NK cells) in HBV mono-infected vs. HBV/HIV-1 co-infected individuals. Methods Total PBMC and subsets isolated from 14 HBV mono-infected (4/14 before and after anti-HBV therapy) and 6 HBV/HIV-1 co-infected individuals (5/6 consistently on dual active anti-HBV/HIV therapy) were tested for HBV genomes, including replication indicative HBV covalently closed circular (ccc)-DNA, by nested PCR/nucleic hybridization and/or quantitative PCR. In CD4+, and/or CD56+ subsets from two HBV monoinfected cases, the HBV polymerase/overlapping surface region was analyzed by next generation sequencing. Results All analyzed whole PBMC from HBV monoinfected and HBV/HIV coinfected individuals were HBV genome positive. Similarly, HBV DNA was detected in all target PBMC subsets regardless of antiviral therapy, but was absent from the CD4+ T cell subset from all HBV/HIV-1 positive cases (P<0.04). In the CD4+ and CD56+ subset of 2 HBV monoinfected cases on tenofovir therapy, mutations at residues associated with drug resistance and/or immune escape (i.e., G145R) were detected in a minor percentage of the population. Summary HBV genomes and drug resistant variants were detectable in PBMC subsets from HBV mono-infected individuals. The HBV replicates in PBMC subsets of HBV/HIV-1 patients except the CD4+ T cell subpopulation.
Highlights
Hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) co-infection is common due to shared modes of transmission with an estimated 4 million co-infected people worldwide [1]
The aim of this study was to compare the presence of hepatitis B virus (HBV) genomes within whole and immune cell subsets from HBV mono-infected and/or HBV/HIV-1 coinfected individuals
In the current study we found HBV DNA, HBV closed circular DNA (cccDNA) and messenger RNA (mRNA) in both whole peripheral blood mononuclear cells (PBMC) isolated from HBV mono-infected and in HBV/HIV-1 co-infected patients on dual-active anti-HBV/ HIV therapy
Summary
Hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) co-infection is common due to shared modes of transmission with an estimated 4 million co-infected people worldwide [1]. In the closely related woodchuck animal model of HBV, woodchuck hepatitis virus (WHV) infection can be completely restricted to the lymphatic system and WHV invasion of lymphoid cells is related to the viral load [6,7]. HBV genomes are detectable in peripheral blood mononuclear cells (PBMC)s from HBV mono-infected patients despite suppressive anti-HBV nucleos/tide analog (NA) therapy [8], in patients after resolution of acute hepatitis B with HBV surface antigen (HBsAg) clearance [9,10], and in circulating transplacental PBMC from HBV positive mothers possibly leading to in utero infection of the neonate [11]. HBV genomes and viral proteins have been detected within a variety of immune cell subpopulations and in some reports the virus appears to target B cells and monocytes [15,16,17,18]. Unique HBV variants in PBMCs, including immune escape mutants, have been linked to vaccine failure and recurrence of HBV infection after liver transplant [23,24,25,26,27]
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