Altered gut microbiota is associated with the formation of occult hepatitis B virus infection.

Hepatitis B virus (HBV), a common blood transmission pathogen worldwide, can lead to viral hepatitis, cirrhosis, liver cancer, and other liver diseases. In particular, occult hepatitis B virus infection (OBI) may be caused by an immune response leading to suppressed virus replication. Gut microbiota can change the immunity status of the human body and, therefore, affect the replication of HBV. Thus, to identify whether there are differences in gut microbiota between HBV carriers and OBI carriers, we collected fecal samples from 18 HBV carriers, 24 OBI blood donors, and also 20 healthy blood donors as negative control. After 16S sequencing, we found that the abundance of Faecalibacterium was significantly reduced in samples from OBI blood donors compared with those from healthy blood donors. Compared with samples from HBV carriers, the samples from OBI blood donors had a significantly increased abundance of Subdoligranulum, which might stimulate immune activation, thus inhibiting HBV replication and contributing to the formation of occult infection. Our findings revealed the potential role of gut microbiota in the formation of OBI and further provided a novel strategy for the treatment of HBV infection.IMPORTANCEOccult hepatitis B virus infection (OBI) is a special form of hepatitis B virus infection with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA negative. Gut microbiota may contribute to the immune response leading to suppressed virus replication and, thus, participates in the development of OBI. The study on gut microbiota of OBI blood donors provides novel data considerably advancing our understanding of the immune mechanism for the determination of occult hepatitis B virus infection, which is helpful for improving the strategy of the treatment of HBV infection.

Molecular characteristics of the full-length genome of occult hepatitis B virus from blood donors in China.

The characteristics of a large sample size of the full-length genome of occult hepatitis B virus (HBV) infection (OBI) have not been extensively explored in China. Voluntary blood donors who were HBsAg-negative/HBV NAT-positive (HBsAg-/HBV NAT+) were identified by blood screening and recruited. Blood samples were tested for HBV serologic markers, viral loads, and PCR to identify OBI. HBV full-length genomes were obtained by amplifying two fragments using nested PCR. The characterization of OBI strains was based on sequence analyses compared with HBsAg+ strains obtained from the same donor population. Of the 50 full-length genomes of 172 identified OBI strains, 33 were classified as genotype B (OBIB) and 17 strains as genotype C (OBIC). Significantly higher nucleotide variabilities were observed in the Pre-S2/S promoter region (SP2) and core upstream regulatory sequence (CURS) in OBIB than in their HBsAg+ controls (P < 0.05). Both OBIB and OBIC showed higher amino acid (aa) variabilities in Pol and Pre-S/S regions than their controls (P < 0.05). In addition, 19 novel OBI-related mutations were found spanning the four open reading frames (ORFs) of the HBV genome. Four novel deletions and one novel insertion were also found in OBIC strains. Several novel OBI-related mutations spanning the four ORFs of the virus were identified by characterizing a large sample size of the full-length OBI genome, which may affect the production of HBsAg and contribute to the occult infection of HBV.

Complete genome sequencing and evolutionary analysis of hepatitis C virus subtype 6a, including strains from Guangdong Province, China.

We performed an evolutionary analysis using whole genome sequence isolates of hepatitis C virus (HCV) 6a from Guangdong Province and reference sequences from various countries. Less than 5% of the HCV genome was found to be under positive selection. The E1 and E2 proteins had the highest proportion of positively selected sites both within and outside of CD8 T cell epitopes in all of the strains. Regions corresponding to CD8 T cell epitopes were under negative selection except in the isolates from Guangdong. Furthermore, we found evidence of three introductions of the virus into Guangdong from Vietnam and other Southeast Asian countries. Thus, this study provides information about the transmission of HCV 6a by comparison of full-length sequences, indicating the impact of selective constraints in Guangdong and across China.