Mutations associated with occult hepatitis B in HIV‐positive South Africans

Powell, Eleanor A.; Gededzha, Maemu P.; Rentz, Michael F.; Rakgole, Nare J.; Selabe, Selokela G.; Seleise, Tebogo A.; Mphahlele, M. Jeffrey; Blackard, Jason T.

doi:10.1002/jmv.24057

Cited by 26 publications

(41 citation statements)

References 80 publications

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“…Occultassociated mutations were identified as described previously (Powell et al, 2014). Briefly, the surface and polymerase open reading frames were sequenced from 30 patients with occult HBV and 19 patients with chronic HBV from HIV-positive South Africans.…”

Section: Methodsmentioning

confidence: 99%

“…We previously identified 235 occult-associated mutations in HIV-positive South Africans (Powell et al, 2014). This population has an extremely high rate of occult HBV -8-23 % compared to 0.8-2.3 % of HIV-negative South Africansthough rates of chronic HBV do not differ greatly by HIV status (Bell et al, 2012;Firnhaber et al, 2011;Lukhwareni et al, 2009;Mphahlele et al, 2006;Powell et al, 2014).…”

Section: Introductionmentioning

confidence: 98%

“…This population has an extremely high rate of occult HBV -8-23 % compared to 0.8-2.3 % of HIV-negative South Africansthough rates of chronic HBV do not differ greatly by HIV status (Bell et al, 2012;Firnhaber et al, 2011;Lukhwareni et al, 2009;Mphahlele et al, 2006;Powell et al, 2014). The aim of this study was to determine the effect of the occultassociated mutations identified in this population that occur in the 'a' determinant, the region of HBsAg where antibody binding occurs.…”

Section: Introductionmentioning

confidence: 99%

“…However, a subset of patients are infected with HBV but do not have detectable HBsAg in their serum and are said to have occult HBV -defined by the presence of HBV DNA in patient serum in the absence of HBsAg (Said, 2011). Anti-HBc and/or anti-HBs antibodies are not reliable for distinguishing occult from chronic infection, as 20-46 % of people with occult HBV have no detectable serological markers of HBV (Hollinger & Sood, 2010;Powell et al, 2014). Because of these factors, occult HBV infection often remains undiagnosed and is rarely treated.…”

Section: Introductionmentioning

confidence: 99%

“…Occult HBV also occurs more frequently in people with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV), suggesting that viral co-infections play a role (Cacciola et al, 1999;Kao et al, 2002;Mphahlele et al, 2006;Shire et al, 2004). Multiple studies have identified viral mutations that are associated with occult HBV and alter the ability of HBsAg to be produced, secreted from the cell or detected by commercial assays (Araujo et al, 2008;Candotti et al, 2006;Chaudhuri et al, 2004;Martin et al, 2010;Powell et al, 2014;Svicher et al, 2012). Though many occult HBV-associated mutations have been identified throughout the viral genome, functional analysis of these mutations is rare.…”

Section: Introductionmentioning

confidence: 99%

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Functional analysis of ‘a’ determinant mutations associated with occult HBV in HIV-positive South Africans

Powell

Boyce

Gededzha

et al. 2016

Journal of General Virology

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Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in the absence of hepatitis B surface antigen (HBsAg). Occult HBV is associated with the development of hepatocellular carcinoma, reactivation during immune suppression, and virus transmission. Viral mutations contribute significantly to the occult HBV phenotype. Mutations in the 'a' determinant of HBsAg are of particular interest, as these mutations are associated with immune escape, vaccine escape and diagnostic failure. We examined the effects of selected occult HBV-associated mutations identified in a population of HIV-positive South Africans on HBsAg production in vitro. Mutations were inserted into two different chronic HBV backbones and transfected into a hepatocyte-derived cell line. HBsAg levels were quantified by enzymelinked immunosorbent assay (ELISA), while the detectability of mutant HBsAg was determined using an HA-tagged HBsAg expression system. Of the seven mutations analysed, four (S132P, C138Y, N146D and C147Y) resulted in decreased HBsAg expression in one viral background but not in the second viral background. One mutation (N146D) led to a decrease in HBsAg detected as compared to HA-tag, indicating that this mutation compromises the ability of the ELISA to detect HBsAg. The contribution of occult-associated mutations to the HBsAg-negative phenotype of occult HBV cannot be determined adequately by testing the effect of the mutation in a single viral background, and rigorous analysis of these mutations is required.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Functional analysis of ‘a’ determinant mutations associated with occult HBV in HIV-positive South Africans

Powell

Boyce

Gededzha

et al. 2016

Journal of General Virology

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Impact of length of replication competent genome of hepatitis B virus over the differential antigenic secretion

Amir

Siddiqui

Farooqui

et al. 2019

J of Cellular Biochemistry

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Hepatitis B virus (HBV) genome consists of circular partially double stranded DNA of 3.2 kb size which gets converted into covalently closed circular DNA (cccDNA) during its life cycle. It then acts as a template for formation of pregenomicRNA (pgRNA) of 3.5 kb. Absence of appropriate animal models prompted a need to establish a better in vitro culture system to uncover the propagation and survival mechanisms of the virus. There is scarcity of data to represent the significance of varying length of replication competent viral genome on the secretion of viral secretory proteins/antigens and in turn on the overall effects on the accomplishment of the viral life cycle. The present study was undertaken to ascertain a suitable replication competent construct in which the viral life cycle of HBV with varying clinical relevance can be studied efficiently. Two constructs (pHBV 1.3 and pHBV 1X) of different sizes were used to transfect hepatoma cells and consequently the secretory antigens were monitored. In vector free approach (pHBV 1X), 3.2 kb viral DNA is directly transfected in the culture system whereas in vector mediated approach more than full length of viral genome is cloned in a vector (pHBV 1.3X) and transfected to obtain a 3.5 kb pgRNA intermediate. HBV secretes two important antigens; HBsAg and HBeAg. HBsAg is a hallmark of infection and is the first to be secreted in the blood stream whereas HBeAg is a secretory protein and remains associated with the viral replication. The construct pHBV 1.3X referring to as more than full length, by virtue of being capable of undergoing transcription without the synthesis of cccDNA intermediate (unlike the clinical situation where an intermediate step of cccDNA synthesis is an essential component to initiate the viral life cycle) appears to be better system for studying viral life cycle in in vitro culture system. The reasons could be assigned to the fact that as low as 100 ng of viral DNA was shown to quantify the replicative phenotypes with this construct. The better efficiency of this construct at prima facie, appears to be mediated through the significantly higher levels of pgRNA transcript during the viral life cycle.

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Prevalence of hepatitis B markers in Senegalese HIV‐1‐infected patients

Lô

Sow

Diop-Ndiaye

et al. 2015

Journal of Medical Virology

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The study aimed to estimate the prevalence of Hepatitis B virus (HBV) infection and to describe the HBV virological profiles among Senegalese HIV-1-infected patients. We conducted a retrospective study between 2006 and 2010 among Senegalese HIV-1-infected patients from the antiretroviral therapy cohort. Samples were screened using Determine(®) HBsAg or MONOLISA(®) POC test. The HBsAg positivity status was confirmed by Architect(®) HBsAg. Detection of HBeAg, anti-HBe Ab, and HBV DNA load were done for the HBsAg-positive samples. Then, Anti-HBcAb was tested for the HBsAg-negative samples. Microsoft Excel was used for data collection and statistical analyses were performed using Epi info 3.5.1. Overall, 466 HIV-infected patients were enrolled including 271 women (58.4%), and 193 men (41.6%) with a median age of 39 years (19-74 years). The global prevalence of HIV/HBV coinfection (HBsAg positive) was 8.8% (41/466). For HBsAg positives samples, the prevalence of HBeAg and the anti-HBeAb were, respectively, 24.4 and 69.2% and the median of HBV DNA viral load, for 27 HBsAg-positive samples, was 3.75 log10 copies/ml. The virological profiles were the following: 7, 15, and 5 patients infected, respectively, by a replicative virus, an inactive virus and a probably mutant virus. For HBsAg-negative samples, 83 out of 109 were positive for anti-HBcAb. This study showed a significant decrease of the prevalence of HBV/HIV coinfection between 2004 and 2014 (P = 0.003), which highlighted the performance of the Senegalese HBV vaccine program. However, implementing a systematic quantification of HBV DNA viral load could improve the monitoring of HBV-infected patient.

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Mutations associated with occult hepatitis B in HIV‐positive South Africans

Cited by 26 publications

References 80 publications

Functional analysis of ‘a’ determinant mutations associated with occult HBV in HIV-positive South Africans

Functional analysis of ‘a’ determinant mutations associated with occult HBV in HIV-positive South Africans

Impact of length of replication competent genome of hepatitis B virus over the differential antigenic secretion

Prevalence of hepatitis B markers in Senegalese HIV‐1‐infected patients

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