scholarly journals Detection of Q129H Immune Escape Mutation in Apparently Healthy Hepatitis B Virus Carriers in Southwestern Nigeria

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1273
Author(s):  
Olufisayo Adeyemi Adesina ◽  
Olusola Anuoluwapo Akanbi ◽  
Oluyinka Oladele Opaleye ◽  
Margaret Oluwatoyin Japhet ◽  
Bo Wang ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Immune Escape ◽  
Escape Mutation ◽  
Resistance Mutations ◽  
Serum Samples ◽  
Hbv Genotype ◽  
Southwestern Nigeria ◽  
Treatment And Prevention ◽  
First Time ◽  
Apparently Healthy

As the global effort to eradicate hepatitis B continues, immune escape mutations (IEMs) and drug resistance mutations (DRMs) affecting its diagnosis, treatment, and prevention are compromising this goal. However, knowledge about the prevalence and circulation of these mutations in Nigeria is scarce. Serum samples (n = 199) from apparently healthy prospective blood donors, pregnant women, and individuals presenting with fever in southwestern Nigeria were analyzed for the presence of IEMs and DRMs by means of nested PCR in the HBV S (HBs) and HBV polymerase (Pol) genes, followed by phylogenetic and mutational analyses. In total, 25.1% (n = 50/199) of samples were positive for HBV, as measured by PCR. In 41 samples (20.6%), both fragments could be amplified, whereas the HBs gene and the Pol gene fragment alone were detected in 0.5% (n = 1/199) and 4% (n = 8/199) of samples, respectively. Sequences were successfully obtained for all 42 HBs gene fragments but for only 31/49 Pol gene fragments (totaling 73 sequences from 44 individuals). All sequences were identified as HBV genotype E. IEMs were present in 18.2% (n = 8/44) of the sequences of HBV-positive individuals with available sequences. IEM Q129H was detected in eight out of the 44 (18.2%) HBV isolates sequenced in this study; however, no DRMs were observed. This study confirms the circulation of HBV IEMs and reports the presence of Q129H IEM for the first time in Nigeria. Intensified research on the dynamics of IEM is necessary in order to enhance the elimination of HBV.

scholarly journals Frequency of Hepatitis B Virus Resistance Mutations in Women Using Tenofovir Gel as Pre-Exposure Prophylaxis

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 569
Author(s):  
Cheryl Baxter ◽  
Sinaye Ngcapu ◽  
Jason T Blackard ◽  
Eleanor A Powell ◽  
Patricia K Penton ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Systemic Exposure ◽  
Resistance Mutations ◽  
Dosing Regimen ◽  
Hbv Genotype ◽  
B Virus ◽  
Tenofovir Gel ◽  
Exposure Prophylaxis ◽  
The Impact

Intermittent use of a single antiretroviral agent in the presence of a replicating virus could potentially increase the development of antiviral resistance. The pericoital, before-and-after sex, dosing regimen used in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 tenofovir gel trial meant that women who were infected with hepatitis B virus (HBV) were exposed intermittently to tenofovir during their participation. The impact of this dosing regimen on HBV resistance was assessed by amplification of the HBV polymerase region from 37 stored plasma samples of women who were HBV surface antigen positive. All samples belonged to HBV genotype A. None of the known tenofovir resistance mutations (M240V/I, L180M, A194T, V214A, N238T) were identified in any individuals. While it is reassuring that no resistance mutations were found among women using topical tenofovir, the rapidly expanding access to oral tenofovir-containing HIV pre-exposure prophylaxis (PrEP), with higher systemic exposure to the drug, makes monitoring for potential HBV drug resistance important.

scholarly journals Prevalence and characteristics of hepatitis B and D virus infections among HIV-positive individuals in Southwestern Nigeria

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Oluyinka Oladele Opaleye ◽  
Olusola Anuoluwapo Akanbi ◽  
Folakemi Abiodun Osundare ◽  
Bo Wang ◽  
Olufisayo Adesina ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hepatitis B ◽  
Phylogenetic Analyses ◽  
Antiretroviral Drugs ◽  
Hbv Dna ◽  
Hiv Positive ◽  
Resistance Mutations ◽  
Southwestern Nigeria ◽  
Drug Resistance Mutations ◽  
Populations At Risk

Abstract Background Coinfections of HIV-positive individuals with Hepatitis B and D virus (HBV and HDV) are common and can be associated with rapid liver damage. Several antiretroviral drugs for HIV exhibit anti-HBV effect; however, the selection of HBV drug resistance mutations (DRMs) in individuals under HIV antiretroviral therapy (ART) has been reported but rarely in Nigeria. In this study the HBV/HDV prevalence and HBV DRMs in HIV-positive individuals in Southwestern Nigeria were assessed. Methods Plasma samples collected from 310 HIV-positive individuals including 295 ART-experienced and 15 ART-naïve persons attending the HIV clinic in three south-western states of Nigeria between June 2017 and August 2017 were analysed by ELISA for HBsAg and anti-HDV. The presence of HDV RNA and HBV DNA was analysed by (RT)-PCR followed by sequencing and phylogenetic analyses for genotyping. The HBV reverse transcription (RT) region was amplified and sequenced for the analysis of drug resistance mutations. Results Overall, 16.1% (n = 50/310) of the HIV-positive individuals were positive for HBsAg, most of which were ART-experienced (94.0%; n = 47/50). From the 50 HBsAg-positive samples, 72.0% (n = 36/50) were positive for HBV DNA and 16.0% (n = 8/50) had detectable HDV RNA while 5.6% (n = 2/36) of the HBV-DNA positive samples had anti-HDV total antibodies. Sequences were available for 31/36 of the HBV DNA-positive and 3/8 HDV RNA-positive samples. HBV DNA-positive samples were characterised as HBV genotype E infections exclusively, while HDV genotype 1 was detected in the HDV RNA-positive samples. HBV DRMs V173L, L180M, S202I and M204V/I, which are associated with lamivudine resistance, were detected in 32.2% (n = 10/31) of the HBV DNA-positive samples. Most of these mutations (90.0%; n = 9/10) were present in the ART-experienced cohort. Conclusions This study indicates that HBV/HDV coinfections are common in HIV-positive individuals under ART in Nigeria. Furthermore, a high proportion of HBV DRMs which potentially compromise future treatment options were detected, underscoring the need for HBV screening prior to starting ART. Further studies should be performed to monitor a possible increase in the spread of HDV among populations at risk of HIV and HBV infections.

scholarly journals Poultry in Poland as Chlamydiaceae carrier

2017 ◽  
Vol 61 (4) ◽  
pp. 411-419 ◽  
Author(s):  
Monika Szymańska-Czerwińska ◽  
Agata Mitura ◽  
Kinga Zaręba ◽  
Christiane Schnee ◽  
Andrzej Koncicki ◽  
...  
Keyword(s):  
Diagnostic Methods ◽  
Molecular Diagnostic ◽  
Control Group ◽  
Study Group ◽  
Poultry Production ◽  
Serum Samples ◽  
Strain Isolation ◽  
Variable Domains ◽  
First Time ◽  
Apparently Healthy

AbstractIntroduction: The study was conducted to investigate the prevalence and genetic diversity of Chlamydia spp. in poultry in Poland and estimate possible transmission to humans.Material and Methods: Molecular diagnostic methods followed by sequencing and strain isolation were used on cloacal/faecal swabs collected from 182 apparently healthy poultry flocks including chickens, turkeys, ducks, and geese. Serum samples obtained from people exposed (study group) and non-exposed (control group) to birds were tested by complement fixation test to acquire data on Chlamydia spp. antibody level.Results: Overall, 15.9% of the tested flocks were Chlamydiaceae-positive and three Chlamydia spp. were identified. Predominant chlamydial agent found was C. gallinacea occurring in 65.5% of all positive poultry flocks and in 73.0% of positive chicken flocks. The sequences from four chicken flocks were assigned to C. abortus, whereas C. psittaci was confirmed in one duck and one goose flock. The analysis of ompA variable domains revealed at least nine genetic variants of C. gallinacea. Chlamydial antibodies were detected in 19.2% of human serum samples in the study group in comparison with 10.8% in the controls.Conclusion: The obtained results confirm that chlamydiae are common among chicken flocks in Poland with C. gallinacea as a dominant species. Moreover, the presence of C. abortus in chickens is reported here for the first time. Further investigation should focus on possible zoonotic transmission of C. gallinacea and C. abortus as well as potential pathogenic effects on birds’ health and poultry production.

scholarly journals Detection of hepatitis B virus isolates with mutations associated with immune escape mutants among pregnant women in Ibadan, southwestern Nigeria

SpringerPlus ◽  
2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Temitope Oluwasegun Cephas Faleye ◽  
Moses Olubusuyi Adewumi ◽  
Ijeoma Maryjoy Ifeorah ◽  
Ewean Chukwuma Omoruyi ◽  
Solomon Adeleye Bakarey ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pregnant Women ◽  
Immune Escape ◽  
Southwestern Nigeria ◽  
B Virus ◽  
Escape Mutants ◽  
Virus Isolates

scholarly journals Impairment of Hepatitis B Virus Virion Secretion by Single-Amino-Acid Substitutions in the Small Envelope Protein and Rescue by a Novel Glycosylation Site

2010 ◽  
Vol 84 (24) ◽  
pp. 12850-12861 ◽  
Author(s):  
Kiyoaki Ito ◽  
Yanli Qin ◽  
Michael Guarnieri ◽  
Tamako Garcia ◽  
Karen Kwei ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Envelope Protein ◽  
Immune Escape ◽  
Envelope Proteins ◽  
Glycosylation Site ◽  
Single Amino Acid ◽  
Dominant Negative Effect ◽  
Escape Mutation ◽  
B Virus

ABSTRACT Mutations in the S region of the hepatitis B virus (HBV) envelope gene are associated with immune escape, occult infection, and resistance to therapy. We previously identified naturally occurring mutations in the S gene that alter HBV virion secretion. Here we used transcomplementation assay to confirm that the I110M, G119E, and R169P mutations in the S domain of viral envelope proteins impair virion secretion and that an M133T mutation rescues virion secretion of the I110M and G119E mutants. The G119E mutation impaired detection of secreted hepatitis B surface antigen (HBsAg), suggesting immune escape. The R169P mutant protein is defective in HBsAg secretion as well and has a dominant negative effect when it is coexpressed with wild-type envelope proteins. Although the S domain is present in all three envelope proteins, the I110M, G119E, and R169P mutations impair virion secretion through the small envelope protein. Conversely, coexpression of just the small envelope protein of the M133T mutant could rescue virion secretion. The M133T mutation could also overcome the secretion defect caused by the G145R immune-escape mutation or mutation at N146, the site of N-linked glycosylation. In fact, the M133T mutation creates a novel N-linked glycosylation site (131NST133). Destroying this site by N131Q/T mutation or preventing glycosylation by tunicamycin treatment of transfected cells abrogated the effect of the M133T mutation. Our findings demonstrate that N-linked glycosylation of HBV envelope proteins is critical for virion secretion and that the secretion defect caused by mutations in the S protein can be rescued by an extra glycosylation site.

scholarly journals Sequence Analysis of PreS2 Region of Hepatitis B Virus Genotype D Isolates

2021 ◽  
Vol 3 (1) ◽  
pp. 5-11
Author(s):  
Amania Anwar ◽  
Sheeba Murad ◽  
Hajra Sadia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Point Mutations ◽  
Cell Permeability ◽  
Serum Samples ◽  
Virus Genotype ◽  
Hbv Genotype ◽  
Hbv Genotypes ◽  
B Virus

Hepatitis B virus (HBV) is a well known agent of liver diseases. HBV disease burden varies across theglobe with regions from low to high endemicity. Pakistan lies in the intermediate endemic zone, withhigh rate of mortality due to liver disease, cirrhosis and hepatocellular carcinoma. There is a wide rangeof heterogeneity in relation to HBV genotypes and sub-genotypes and in their patterns of pathogenesis,virulence and response to antiviral therapy. A large number of HBV genomic variations are associatedwith clinical outcomes such as hepatocellular carcinoma and liver cirrhosis. Thus, the present study aimsto analyze PreS2 gene sequences from HBV isolates and their phylogeny. To investigate this, a study wasconducted on twenty one HBV chronically infected individuals, serum samples were subjected to PCRwith specific primers for PreS2 region of HBV genotype D and then sequenced. Point mutations: A39V,P41H and L42I were found in cell permeability domain of PreS2 protein. However, MHC class I and IIepitopes were conserved in all sequences. Phylogenetic analysis was carried out by comparing thenucleotide sequence with 22 reference sequences of HBV sub-genotype D retrieved from the GeneBank.Phylogenetic analysis showed that two of our isolates, ASAB1 (2266) and ASAB3 (PIMS 7) sharedcluster 1 with China D1, Pakistan D1, Iran D1 and Turkey D1. Meanwhile, ASAB2 (HF2) was grouped incluster 2 with Lebanese D2 and Brazil D2.

scholarly journals Hepatitis B virus pre-existing drug resistant mutation is related to the genotype and disease progression

2017 ◽  
Vol 11 (09) ◽  
pp. 727-732 ◽  
Author(s):  
Liping Wang ◽  
Fangzheng Han ◽  
Hualing Duan ◽  
Fang Ji ◽  
Xuebing Yan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Hbv Genotype ◽  
B Virus ◽  
Drug Resistant Mutation ◽  
Genotype C ◽  
Resistant Mutation

Introduction: Previous studies have indicated that the drug-resistant mutations of hepatitis B virus (HBV) are a major obstacle to antiviral therapy. However, it is still unclear whether there are pre-existent resistance mutations in patients with HBV infection and the relationship between drug-resistant mutation, genotypes, and progression of hepatitis B disease. Methodology: A total of 357 treatment-naïve patients with HBV infection were involved in this retrospective study. The drug-resistant mutations of HBV reverse transcriptase domain were screened by direct gene sequencing. Results: Lamivudine (LAM) resistance was detected in 8 patients (3.7%) with chronic hepatitis B (CHB), 13 (11.7%) patients with liver cirrhosis (LC), and 6 (21.4%) patients with hepatocellular carcinoma (HCC). Adefovir(ADV)-resistant mutations were detected in 10 (4.6%) patients with CHB, 15 (13.5%) patients with  LC and 4 (14.5%) patients with HCC. Both LAM and ADV resistant mutations were detected in 2 patients (0.9%) with CHB, 1 patient (0.9%) with LC and 1 patient (3.6%) with HCC. Significant differences (p <0.01) were observed in the drug-resistance rates among patients with CHB, LC and HCC. Meanwhile, all the drug-resistant mutations were found in patients with HBV genotype C. Conclusions: This study demonstrated higher risk of pre-existing drug-resistant mutations in patients with HBV genotype C comparing to patients with HBV genotype B. Likewise, increasing prevalence of pre-existing drug-resistant mutations was shown, alongside with the progression of the disease.

scholarly journals Detection and circulation of hepatitis B virus immune escape mutants among asymptomatic community dwellers in Ibadan, southwestern Nigeria

2015 ◽  
Vol 39 ◽  
pp. 102-109 ◽  
Author(s):  
Temitope Oluwasegun Cephas Faleye ◽  
Olubusuyi Moses Adewumi ◽  
Ijeoma Maryjoy Ifeorah ◽  
Adegboyega Akere ◽  
Adeleye Solomon Bakarey ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Southwestern Nigeria ◽  
B Virus ◽  
Escape Mutants ◽  
Community Dwellers

scholarly journals Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region

2020 ◽  
Vol 11 ◽  
Author(s):  
Natalia M. Araujo ◽  
Sheila A. Teles ◽  
Natália Spitz
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Large Scale ◽  
Immune Escape ◽  
Diagnostic Procedures ◽  
Relevant Information ◽  
Geographic Region ◽  
Antiviral Resistance ◽  
Hbv Genotype ◽  
B Virus

Hepatitis B virus (HBV) is a highly variable DNA virus due to its unique life cycle, which involves an error-prone reverse transcriptase. The high substitution rate drives the evolution of HBV by generating genetic variants upon which selection operates. HBV mutants with clinical implications have been documented worldwide, indicating the potential for spreading and developing their own epidemiology. However, the prevalence of such mutants among the different HBV genotypes and subgenotypes has not been systematically analyzed. In the current study, we performed large-scale analysis of 6,479 full-length HBV genome sequences from genotypes A-H, with the aim of gaining comprehensive insights into the relationships of relevant mutations associated with immune escape, antiviral resistance and hepatocellular carcinoma (HCC) development with HBV (sub)genotypes and geographic regions. Immune escape mutations were detected in 10.7% of the sequences, the most common being I/T126S (1.8%), G145R (1.2%), M133T (1.2%), and Q129R (1.0%). HBV genotype B showed the highest rate of escape mutations (14.7%) while genotype H had no mutations (P &lt; 0.001). HCC-associated mutations were detected in 33.7% of the sequences, with significantly higher frequency of C1653T, T1753V and A1762T/G1764A in genotype G than C (P &lt; 0.001). The overall frequencies of lamivudine-, telbivudine-, adefovir-, and entecavir-resistant mutants were 7.3, 7.2, 0.5, and 0.2%, respectively, while only 0.05% showed reduced susceptibility to tenofovir. In particular, the highest frequency of lamivudine-resistant mutations was observed in genotype G and the lowest frequency in genotype E (32.5 and 0.3%; P &lt; 0.001). The prevalence of HBV mutants was also biased by geographic location, with North America identified as one of the regions with the highest rates of immune escape, antiviral resistance, and HCC-associated mutants. The collective findings were discussed in light of natural selection and the known characteristics of HBV (sub)genotypes. Our data provide relevant information on the prevalence of clinically relevant HBV mutations, which may contribute to further improvement of diagnostic procedures, immunization programs, therapeutic protocols, and disease prognosis.

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