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Discovery of a Novel Mutation (X8Del) Resulting in an 8-bp Deletion in the Hepatitis B Virus X Gene Associated with Occult Infection in Korean Vaccinated Individuals.

Kim H, Gong JR, Lee SA, Kim BJ - PLoS ONE (2015)

Bottom Line: The presence of HBV DNA was confirmed in 6 subjects (6.9%).Our in vitro and in vivo analyses using the full-length HBV genome indicated that the X8Del HBxAg variant reduced the secretion of HBsAg and HBV virions compared to the wild type.In conclusion, our data suggest that a novel mutation (X8Del) may contribute to occult HBV infection in Korean vaccinated individuals via a reduced secretion of HBsAg and virions, possibly by compromising HBxAg's transacting capacity.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, Seoul, Korea.

ABSTRACT
Universal infantile hepatitis B virus (HBV) vaccination may lead to an increase in vaccine escape variants, which may pose a threat to the long-term success of massive vaccination. To determine the prevalence of occult infections in Korean vaccinated individuals, 87 vaccinated subjects were screened for the presence of HBV DNA using both the nested PCR protocol and the VERSANT HBV DNA 3.0 assay. The mutation patterns of variants were analyzed in full-length HBV genome sequences. Their HBsAg secretion and replication capacities were investigated using both in vitro transient transfection and in vivo hydrodynamic injection. The presence of HBV DNA was confirmed in 6 subjects (6.9%). All six variants had a common mutation type (X8Del) composed of an 8-bp deletion in the C-terminal region of the HBV X gene (HBxAg). Our in vitro and in vivo analyses using the full-length HBV genome indicated that the X8Del HBxAg variant reduced the secretion of HBsAg and HBV virions compared to the wild type. In conclusion, our data suggest that a novel mutation (X8Del) may contribute to occult HBV infection in Korean vaccinated individuals via a reduced secretion of HBsAg and virions, possibly by compromising HBxAg's transacting capacity.

No MeSH data available.


Related in: MedlinePlus

The location of a novel mutation (XDel8) that resulted in the deletion of eight nucleotides (nt 396 to 404) in the C-terminus of the X region found in the 6 vaccinated subjects proven to be HBV DNA positive.
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pone.0139551.g002: The location of a novel mutation (XDel8) that resulted in the deletion of eight nucleotides (nt 396 to 404) in the C-terminus of the X region found in the 6 vaccinated subjects proven to be HBV DNA positive.

Mentions: To identify mutations related to HBV occult infection from vaccinated individuals, HBV complete genome sequences were analyzed from the 6 subjects with HBV DNA-positive results. To this end, a total of 11 overlapped PCR products covering all of the HBV genome were amplified by nested PCR from 6 subjects and sequenced (Fig 1). Phylogenetic analysis based on complete HBV genome sequences showed that the HBV strains from all 6 subjects belonged to genotype C2 (Fig 2). The mutation patterns of the full-length HBV genome region compared to the reference strains are presented in Table 2. Notably, all 6 subjects had a common mutation type consisting of the deletion of eight nucleotides (nt 396 to 404) in the C-terminus of the X region (hereafter, XDel8) (Fig 3). Moreover, the F220L mutation in the small surface region (HBsAg) that leads to the L575V mutation in the same overlapping polymerase region was found in two samples (SS-3-22 and SS-4-15). Finally, the T106S mutation in the HBV X region (HBxAg) was detected in two samples (SS-3-22 and SS-7-5) (Table 2). In the current study, we focused on X8Del as a novel mutation leading to occult infection in Korean vaccinated subjects because it was present in all of the HBV DNA-positive vaccine subjects.


Discovery of a Novel Mutation (X8Del) Resulting in an 8-bp Deletion in the Hepatitis B Virus X Gene Associated with Occult Infection in Korean Vaccinated Individuals.

Kim H, Gong JR, Lee SA, Kim BJ - PLoS ONE (2015)

The location of a novel mutation (XDel8) that resulted in the deletion of eight nucleotides (nt 396 to 404) in the C-terminus of the X region found in the 6 vaccinated subjects proven to be HBV DNA positive.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4593592&req=5

pone.0139551.g002: The location of a novel mutation (XDel8) that resulted in the deletion of eight nucleotides (nt 396 to 404) in the C-terminus of the X region found in the 6 vaccinated subjects proven to be HBV DNA positive.
Mentions: To identify mutations related to HBV occult infection from vaccinated individuals, HBV complete genome sequences were analyzed from the 6 subjects with HBV DNA-positive results. To this end, a total of 11 overlapped PCR products covering all of the HBV genome were amplified by nested PCR from 6 subjects and sequenced (Fig 1). Phylogenetic analysis based on complete HBV genome sequences showed that the HBV strains from all 6 subjects belonged to genotype C2 (Fig 2). The mutation patterns of the full-length HBV genome region compared to the reference strains are presented in Table 2. Notably, all 6 subjects had a common mutation type consisting of the deletion of eight nucleotides (nt 396 to 404) in the C-terminus of the X region (hereafter, XDel8) (Fig 3). Moreover, the F220L mutation in the small surface region (HBsAg) that leads to the L575V mutation in the same overlapping polymerase region was found in two samples (SS-3-22 and SS-4-15). Finally, the T106S mutation in the HBV X region (HBxAg) was detected in two samples (SS-3-22 and SS-7-5) (Table 2). In the current study, we focused on X8Del as a novel mutation leading to occult infection in Korean vaccinated subjects because it was present in all of the HBV DNA-positive vaccine subjects.

Bottom Line: The presence of HBV DNA was confirmed in 6 subjects (6.9%).Our in vitro and in vivo analyses using the full-length HBV genome indicated that the X8Del HBxAg variant reduced the secretion of HBsAg and HBV virions compared to the wild type.In conclusion, our data suggest that a novel mutation (X8Del) may contribute to occult HBV infection in Korean vaccinated individuals via a reduced secretion of HBsAg and virions, possibly by compromising HBxAg's transacting capacity.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, Seoul, Korea.

ABSTRACT
Universal infantile hepatitis B virus (HBV) vaccination may lead to an increase in vaccine escape variants, which may pose a threat to the long-term success of massive vaccination. To determine the prevalence of occult infections in Korean vaccinated individuals, 87 vaccinated subjects were screened for the presence of HBV DNA using both the nested PCR protocol and the VERSANT HBV DNA 3.0 assay. The mutation patterns of variants were analyzed in full-length HBV genome sequences. Their HBsAg secretion and replication capacities were investigated using both in vitro transient transfection and in vivo hydrodynamic injection. The presence of HBV DNA was confirmed in 6 subjects (6.9%). All six variants had a common mutation type (X8Del) composed of an 8-bp deletion in the C-terminal region of the HBV X gene (HBxAg). Our in vitro and in vivo analyses using the full-length HBV genome indicated that the X8Del HBxAg variant reduced the secretion of HBsAg and HBV virions compared to the wild type. In conclusion, our data suggest that a novel mutation (X8Del) may contribute to occult HBV infection in Korean vaccinated individuals via a reduced secretion of HBsAg and virions, possibly by compromising HBxAg's transacting capacity.

No MeSH data available.


Related in: MedlinePlus