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Mutations associated with occult hepatitis B in HIV-positive South Africans.

ABSTRACT: Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV-positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult-associated mutations-those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references-were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult-associated mutations were identified. Ten occult-associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult-associated mutations at the same residue. Occult-associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro.

SUBMITTER: Powell EA

PROVIDER: S-EPMC4562318 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Mutations associated with occult hepatitis B in HIV-positive South Africans.

Powell Eleanor A EA Gededzha Maemu P MP Rentz Michael M Rakgole Nare J NJ Selabe Selokela G SG Seleise Tebogo A TA Mphahlele M Jeffrey MJ Blackard Jason T JT

Journal of medical virology 20140827 3

Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, althoug ...[more]

PMID: 25164924

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Project description:ObjectivesHLA-G, part of the major histocompatibility complex (MHC), is associated with the risk of developing preeclampsia (PE). In this study, we determined the contribution of specific HLA-G polymorphisms on the risk of developing preeclampsia in HIV-infected and uninfected South Africans of African ancestry.MethodsOne hundred and ninety-three women of African ancestry were enrolled (74 HIV-uninfected normotensive, 60 HIV-infected normotensive, 34 HIV-uninfected, and 25 HIV-infected preeclamptics). Sanger sequencing of the untranslated region was performed to genotype six SNPs, i.e., 14 bp Ins/Del of rs66554220, rs1710, rs1063320, rs1610696, rs9380142, and rs1707).ResultsFor rs66554220, we have the following results: (a) based on pregnancy type-the Ins/Ins and Del/Ins genotype frequency was higher in preeclampsia (PE) compared to normotensive pregnancies (Ins/Ins vs. Del/Ins, P = 0.02∗: OR (95%CI) = 13.44 (0.7222-249.9); Del/Del vs. Del/Ins, P = 0.03∗: OR (95%CI) = 2.95 (1.10-7.920)); (b) based on HIV status-the Ins/Ins showed both genotypic and allelic association with HIV infection. HIV-infected PE has higher Ins/Ins genotypic and allelic frequencies compared to HIV-uninfected PE (Ins/Ins vs. Del/Ins, P = 0.005∗∗: OR (95%CI) = 21.32 (1.71-4.17); Ins, P = 0.005∗∗; OR (95%IC) = 21.32 (1.71-4.17)). For rs1707, we have the following results: (a) based on pregnancy type-there were CT genotypic frequencies in PE, more especially LOPE compared to normotensive pregnancies (TT vs. CT, P = 0.0092∗∗: OR (95%CI) = 5.(1.39 - 25.64)), and no allelic association was noted; (b) based on HIV status-CT was higher in HIV-infected LOPE compared to uninfected LOPE (TT vs. TC, P = 0.0006∗∗∗: OR (95%CI) = 40.00 (2.89 - 555.1)). For rs1710 and rs1063320, no significant differences in the genotype and allele frequencies were noted based on pregnancy type and HIV status. For rs9380142, we have the following results: (a) based on pregnancy type-no significant differences were noted between normotensive compared to PE pregnancies; (b) based on HIV status-AA genotypes occurred more in the HIV-infected PE group (AA vs. GG, P = 0.02∗: OR (95%CI) = 13.97 (0.73 - 269.4)), while A allelic frequency occurred more in HIV-infected PE, especially LOPE compared to uninfected groups (A vs. G, P = 0.0003∗∗∗: OR (95%CI) = 10.72 (2.380 - 48.32); P = 0.02∗: OR (95%CI) = 9.00 (1.07 - 75.74)). For rs1610696, we have the following results: (a) based on pregnancy type-genotypic and allelic frequencies of CC were higher in PE compared to normotensive pregnancies (CC vs. GG, P = 0.0003∗∗∗: OR (95%CI) = 31.87 (1.861 - 545.9); C, P = 0.0001∗∗∗: OR (95%IC) = 21.91 (2.84 - 169.0)); (b) based on HIV status-GG frequencies were higher in the HIV-infected PE more especially LOPE groups (GG vs. GC, P = 0.02∗: OR (95%CI) = 16.87 (0.81 - 352.1); GG vs. CC, P = 0.0001∗∗∗: OR (95%CI) = 159.5 (13.10 - 1942)).ConclusionSelected HLA-G 14 bp polymorphisms (Ins/Ins) and genotypic and allelic differences in rs9380142, rs1610696, and rs1707 are associated with the pathogenesis of preeclampsia in HIV-infected South African women of African ancestry. More genetic studies evaluating the association between preeclampsia and HIV infection are needed to improve diagnosis and antenatal care.

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Mutations associated with occult hepatitis B in HIV-positive South Africans.

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Mutations associated with occult hepatitis B in HIV-positive South Africans.

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