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Phylogeography of hepatitis B virus: The role of Portugal in the early dissemination of HBV worldwide.

ABSTRACT: In Portugal, the genetic diversity, origin of HBV and the Portuguese role in the dissemination of HBV worldwide were never investigated. In this work, we studied the epidemic history and transmission dynamics of HBV genotypes that are endemic in Portugal. HBV pol gene was sequenced from 130 patients followed in Lisbon. HBV genotype A was the most prevalent (n = 54, 41.5%), followed by D (n = 44, 33.8%), and E (n = 32, 24.6%). Spatio-temporal evolutionary dynamics was reconstructed in BEAST using a Bayesian Markov Chain Monte Carlo method, with a GTR nucleotide substitution model, an uncorrelated lognormal relaxed molecular clock model, a Bayesian skyline plot, and a continuous diffusion model. HBV subgenotype D4 was the first to be introduced in Portugal around 1857 (HPD 95% 1699-1931) followed by D3 and A2 a few decades later. HBV genotype E and subgenotype A1 were introduced in Portugal later, almost simultaneously. Our results indicate a very important role of Portugal in the exportation of subgenotypes D4 and A2 to Brazil and Cape Verde, respectively, in the beginning of the XX century. This work clarifies the epidemiological history of HBV in Portugal and provides new insights in the early and global epidemic history of this virus.

SUBMITTER: Marcelino R

PROVIDER: S-EPMC9778982 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Phylogeography of hepatitis B virus: The role of Portugal in the early dissemination of HBV worldwide.

Marcelino Rute R Marcelino Rute R Ezeonwumelu Ifeanyi Jude IJ Janeiro André A Mimoso Paula P Matos Sónia S Briz Veronica V Pimentel Victor V Pingarilho Marta M Tato Marinho Rui R Maria Marcelino José J Taveira Nuno N Abecasis Ana A

PloS one 20221222 12

In Portugal, the genetic diversity, origin of HBV and the Portuguese role in the dissemination of HBV worldwide were never investigated. In this work, we studied the epidemic history and transmission dynamics of HBV genotypes that are endemic in Portugal. HBV pol gene was sequenced from 130 patients followed in Lisbon. HBV genotype A was the most prevalent (n = 54, 41.5%), followed by D (n = 44, 33.8%), and E (n = 32, 24.6%). Spatio-temporal evolutionary dynamics was reconstructed in BEAST using ...[more]

PMID: 36548381

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Project description:The same entry pathway is shared by HBV and HDV. Both viruses attach to hepatocytes via heparansulfate proteoglycan and utilize sodium taurocholate co-transporting polypeptide (NTCP) for a specifc entry. This specific entry step is inhibited by Myrcludex B, a 47-aa lipopeptide myristoylated at the N-terminus. Here we compared the cellular response in the gene expression level triggerred by both viruses. The microarray data shows that HBV infection leads to a silent response but HDV infection triggers high level of innate response such as inteferon-stimulated genes (ISG) expression. Moreover, the response depends on the hepatic cell lines used for infection. Compared to HepG2 cells, HuH7 can not induce ISG even infected by HDV. Abstract of manuscript: Background & aims: Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify the responsible sensor and evaluate the effect of IFN on HDV replication. Methods: HDV and HBV susceptible hepatoma cell lines and primary human hepatocytes (PHH) were used for infection studies. Viral markers and cellular gene expression were analyzed at different time points after infection. Pattern recognition receptors (PRRs) required for HDV-mediated IFN activation and the impact on HDV replication were studied using stable knock-down or overexpression of the PRRs. Results: Microarray analysis revealed that HDV but not HBV infection activated a broad range of interferon stimulated genes (ISGs) in HepG2NTCP cells. HDV strongly activated IFN-β and IFN-λ in cell lines and PHH. HDV induced IFN levels remained unaltered upon RIG-I or TLR3 knock-down, but were almost completely abolished upon MDA5 depletion. Conversely, overexpression of MDA5 but not RIG-I and TLR3 in Huh7.5NTCP cells partially restored ISG induction. During long-term infection, IFN levels gradually diminished in both HepG2NTCP and HepaRGNTCP cell lines. MDA5 depletion had little effect on HDV replication despite dampening HDV-induced IFN response. Moreover, treatment with type I or type III IFNs did not abolish HDV replication. Conclusions: Active replication of HDV induces an IFN-β/λ response, which is predominantly mediated by MDA5. This IFN response and exogenous IFN treatment have only a moderate effect on HDV replication in vitro indicating the adaption of HDV replication to an IFN activated state.

Dataset Information

Phylogeography of hepatitis B virus: The role of Portugal in the early dissemination of HBV worldwide.

Publications

Phylogeography of hepatitis B virus: The role of Portugal in the early dissemination of HBV worldwide.

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