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1.
J Clin Virol ; 150-151: 105159, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1851455

ABSTRACT

BACKGROUND: Chronic hepatitis B virus (HBV) treatment consists of nucleos(t)ide analogues to suppress viral replication. The HBV inhibitor tenofovir has a high barrier to resistance, however, evidence of virus-escape is emerging. This study investigates HBV evolution in patients undergoing tenofovir treatment with the primary aim to assess the emergence of putative resistance mutations. METHODS: HBV DNA was extracted from blood samples of two patients with HBeAg-positive chronic HBV infection and persistent viremia despite tenofovir treatment, and subsequently amplified by PCR before full-length HBV genomes were assembled by deep sequencing. The mutation linkage within the viral population was evaluated by clonal analysis of amplicons. RESULTS: Sequence analysis of HBV, derived from 11 samples collected 2010-2020 from one patient, identified 12 non-synonymous single-nucleotide polymorphisms (SNPs) emerging during a tenofovir treatment interruption from 2014 to 2017. Two of the SNPs were in the reverse transcriptase (RT; H35Q and D263E). The two RT mutations were linked and persisted despite restarting tenofovir treatment in 2017. For the second patient, we analyzed HBV derived from six samples collected 2014-2020 following 10 years of tenofovir treatment, and identified five non-synonymous SNPs, that confer resistance towards entecavir and/or lamivudine. Two RT mutations (H35N and P237T) emerged during subsequent 5-year entecavir treatment. H35N was maintained during final tenofovir treatment. CONCLUSIONS: Our findings indicate that changes at the conserved residue 35 (H35N/Q) in the HBV RT may be associated with tenofovir resistance. These variants have not previously been described, and further studies are warranted to assess resistance in vitro and in vivo.


Subject(s)
Hepatitis B, Chronic , Organophosphonates , Adenine/adverse effects , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , DNA, Viral/genetics , Drug Resistance, Viral/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Mutation , Organophosphonates/therapeutic use , RNA-Directed DNA Polymerase/genetics , Tenofovir/pharmacology , Tenofovir/therapeutic use , Viremia/drug therapy
2.
Int J Infect Dis ; 118: 141-143, 2022 May.
Article in English | MEDLINE | ID: covidwho-1838856

ABSTRACT

Acute hepatitis B (AHB) is usually asymptomatic, but it can progress to chronic hepatitis B (HB) defined by HB surface antigen (HBsAg) persisting beyond 6 months. Nevertheless, the delay of HBsAg seroclearance is not well-defined. During pregnancy, the immune system of the pregnant women is altered and delayed HBsAg loss can be observed, leading to chronic infection. Here, we present an uncommon case of AHB in a pregnant woman in whom rapid HBsAg seroclearance (52 days after AHB) was associated with a favourable outcome (no injury to liver). This patient received tenofovir disoproxil fumarate promptly after diagnosis. The case raises questions about the use of antiviral treatment in AHB. This is generally not recommended in AHB, but it would be potentially useful in pregnant women to reduce the risk of chronic HB infection and could also prevent the transmission of the maternal precore mutation, thus reducing the significant risk of fulminant hepatitis in the infant. This case also highlights the impact of the hepatitis B virus (HBV) genotype and precore/core mutations on the clinical course of the disease.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Antiviral Agents/therapeutic use , DNA, Viral , Female , Hepatitis B/diagnosis , Hepatitis B/drug therapy , Hepatitis B/prevention & control , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Humans , Infant , Pregnancy
3.
Biosens Bioelectron ; 209: 114165, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1773134

ABSTRACT

Detection of nucleic acids is crucial in many medical applications, and in particular for monitoring infectious diseases, as it has become perfectly clear after the pandemic infection of COVID-19. In this context, the development of innovative detection methods based on signal-amplification rather than analyte-amplification represents a significant breakthrough compared to existing PCR-based methodologies, allowing the development of new nucleic acid detection technologies suitable to be integrated in portable and low-cost sensor devices while keeping high sensitivities, thus enabling massive diagnostic screening. In this work, we present a novel molecular sensor for the ultrasensitive PCR-free detection of Hepatitis B Virus (HBV) based on electrochemiluminescence (ECL). Thanks to the combination of surface cooperative hybridization scheme with ECL detection strategy, our novel DNA sensor is able to detect HBV genome - both synthetic and extracted - with the unprecedented limit of detection (LoD) of 0.05 cps µL-1 for extracted sample, that is even lower than the typical LoD of PCR methodologies. The detection concept presented here for HBV detection is very versatile and can be extended to other pathogens, paving the way for future development of rapid molecular test for infectious diseases, both viral and bacterial, in Point-of-Care (PoC) format.


Subject(s)
Biosensing Techniques , COVID-19 , Communicable Diseases , Biosensing Techniques/methods , COVID-19/diagnosis , Genome, Viral , Hepatitis B virus/genetics , Humans , Polymerase Chain Reaction
4.
Liver Int ; 42(6): 1287-1296, 2022 06.
Article in English | MEDLINE | ID: covidwho-1666331

ABSTRACT

BACKGROUND AND AIMS: The safety and antibody responses of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic hepatitis B (CHB) virus infection is still unclear, and exploration in safety and antibody responses of COVID-19 vaccination in CHB patients is significant in clinical practice. METHODS: 362 adult CHB patients and 87 healthy controls at an interval of at least 21 days after a full-course vaccination (21-105 days) were enrolled. Adverse events (AEs) were collected by questionnaire. The antibody profiles at 1, 2 and 3 months were elucidated by determination of anti-spike IgG, anti-receptor-binding domain (RBD) IgG, and RBD-angiotensin-converting enzyme 2 blocking antibody. SARS-CoV-2 specific B cells were also analysed. RESULTS: All AEs were mild and self-limiting, and the incidence was similar between CHB patients and controls. Seropositivity rates of three antibodies were similar between CHB patients and healthy controls at 1, 2 and 3 months, but CHB patients had lower titers of three antibodies at 1 month. Compared to healthy controls, HBeAg-positive CHB patients had higher titers of three antibodies at 3 months (all P < .05) and a slower decline in antibody titers. Frequency of RBD-specific B cells was positively correlated with titers of anti-RBD IgG (OR = 1.067, P = .004), while liver cirrhosis, antiviral treatment, levels of HBV DNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin (TB) were not correlated with titers of anti-RBD IgG. CONCLUSIONS: Inactivated COVID-19 vaccines were well tolerated, and induced effective antibody response against SARS-CoV-2 in CHB patients.


Subject(s)
COVID-19 , Hepatitis B, Chronic , Adult , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Immunoglobulin G , SARS-CoV-2
6.
J Viral Hepat ; 29(3): 205-208, 2022 03.
Article in English | MEDLINE | ID: covidwho-1532870

ABSTRACT

The COVID-19 pandemic interrupted routine healthcare services. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are often asymptomatic, and therefore, screening and on/post-treatment monitoring are required. Our aim was to determine the effect of the first, second and third waves of the pandemic on HBV and HCV testing in Ontario, Canada. We extracted data from Public Health Ontario for HBV and HCV specimens from 1 January 2019 to 31 May 2021. Testing volumes were evaluated and stratified by age, sex and region. Changes in testing volumes were analysed by per cent and absolute change. Testing volumes decreased in April 2020 with the first wave of the pandemic and recovered to 72%-75% of prepandemic volumes by the end of the first wave. HBsAg testing decreased by 33%, 18% and 15%, and HBV DNA testing decreased by 37%, 27% and 20%, in each consecutive wave. Anti-HCV testing decreased by 35%, 21% and 19%, and HCV RNA testing decreased by 44%, 30% and 36% in each consecutive wave. These trends were consistent by age, region and sex. Prenatal HBV testing volumes were stable. In conclusion, significant decreases in HBV and HCV testing occurred during the first three waves of the pandemic and have not recovered. In addition to direct consequences on viral hepatitis elimination efforts, these data provide insight into the impacts of the pandemic on chronic disease screening and management. Strategies to make up for missed testing will be critical to avoid additional consequences of COVID-19 long after the pandemic has resolved.


Subject(s)
COVID-19 , Hepatitis B , Hepatitis C , Female , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Humans , Ontario/epidemiology , Pandemics , Pregnancy , SARS-CoV-2
7.
Cell Rep ; 36(7): 109530, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1330686

ABSTRACT

A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolve 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV)-positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions by ONT sequencing. That we find no evidence of SARS-CoV-2 integration suggests that such events are, at most, extremely rare in vivo and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus.


Subject(s)
COVID-19/virology , DNA, Viral/genetics , Genome, Human , SARS-CoV-2/genetics , Sequence Analysis, DNA , Virus Integration , Aged , Animals , COVID-19/diagnosis , Carcinoma, Hepatocellular/virology , Chlorocebus aethiops , HEK293 Cells , Hepatitis B virus/genetics , Host-Pathogen Interactions , Humans , Liver Neoplasms/virology , Long Interspersed Nucleotide Elements , Male , Nanopore Sequencing , Vero Cells
8.
Viruses ; 13(7)2021 06 25.
Article in English | MEDLINE | ID: covidwho-1289021

ABSTRACT

The current COVID-19 pandemic has highlighted the urgent need to develop effective therapeutic strategies. We evaluated the in vitro antiviral effect against SARS-CoV-2 of a hepatitis B virus (HBV) hexamer peptide, Poly6, which is capable of eliciting an antiviral effect against human immunodeficiency virus -1 (HIV-1), as a novel HIV-1 integrase inhibitor, and a strong anticancer immune response in an IFN-I-dependent manner, as a novel potential adjuvant in anticancer immunotherapy. Here, we report that Poly6 exerts an anti-SARS-CoV-2 effect, with an estimated 50% inhibitory concentration of 2.617 µM, in the human bronchial epithelial cell line, Calu-3 but not in Vero-E6 cells, which are deficient in type 1 interferon (IFN-I) signaling. We proved via assays based on mRNA profiles, inhibitors, or blocking antibodies that Poly6 can exert an anti-SARS-CoV-2 effect in an IFN-I-dependent manner. We also found that Poly6 inhibits IL-6 production enhanced by SARS-CoV-2 in infected Calu-3 cells at both the transcription and the translation levels, mediated via IL-10 induction in an IFN-I-dependent manner. These results indicate the feasibility of Poly6 as an IFN-I-inducing COVID-19 drug with potent antiviral and anti-inflammatory activities.


Subject(s)
Antiviral Agents/pharmacology , Epithelial Cells/drug effects , Hepatitis B virus/chemistry , Interferon Type I/immunology , Peptides/pharmacology , SARS-CoV-2/drug effects , Virus Replication/drug effects , Animals , Bronchi/cytology , Bronchi/virology , Chlorocebus aethiops , Epithelial Cells/immunology , Epithelial Cells/virology , Hepatitis B virus/genetics , Humans , Lung/cytology , Lung/virology , Peptides/immunology , SARS-CoV-2/immunology , Vero Cells
9.
AIDS Rev ; 22(4): 227-228, 2020 12 23.
Article in English | MEDLINE | ID: covidwho-1006729

ABSTRACT

The clinical spectrum of "Severe Acute Respiratory Syndrome Coronavirus type 2" (SARS-CoV-2) infection is wider than initially thought. The coronavirus does not establish a chronic cellular infection, in contrast with HIV or the hepatitis B virus, that keeps their genomes, respectively, as proviruses integrated within the chromosomes or as episomes (Soriano et al. J Antimicrob Chemother 2014).


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , HIV-1/genetics , HIV-1/pathogenicity , Hepatitis B virus/genetics , Hepatitis B virus/pathogenicity , Humans
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