Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approach
- National and Kapodistrian University of Athens, Greece
- European University of Cyprus, Cyprus
- University of the Witwatersrand, South Africa
Abstract
Hepatitis B virus (HBV) infection constitutes a global public health problem. In order to establish how HBV was disseminated across different geographic regions, we estimated the levels of regional clustering for genotypes D and A. We used 916 HBV-D and 493 HBV-A full-length sequences to reconstruct their global phylogeny. Phylogeographic analysis was conducted by reconstruction of ancestral states using the criterion of parsimony. The putative origin of genotype D was in North Africa/Middle East. HBV-D sequences form low levels of regional clustering for the Middle East and Southern Europe. In contrast, HBV-A sequences form two major clusters, the first including sequences mostly from sub-Saharan Africa, and the second including sequences mostly from Western and Central Europe. Conclusion: We observed considerable differences in the global dissemination patterns of HBV-D and HBV-A and different levels of monophyletic clustering in relation to the regions of prevalence of each genotype.
Data availability
All data (sequence alignments and additional pieces of information related to the accession numbers of sequences and their sampling areas) are available at Dryad (doi: 10.5061/dryad.bt4q242).
-
Data from: Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approachAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Timokratis Karamitros
Dimitrios Paraskevis
Funding
Hellenic Scientific Society for the Study of AIDS and STDs
- Evangelia-Georgia Kostaki
- Timokratis Karamitros
- Garyfallia Stefanou
- Ioannis Mamais
- Konstantinos Angelis
- Angelos Hatzakis
- Anna Kramvis
- Dimitrios Paraskevis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Carla Osiowy, University of Manitoba, Canada
Version history
- Received: April 30, 2018
- Accepted: July 28, 2018
- Accepted Manuscript published: August 7, 2018 (version 1)
- Version of Record published: August 31, 2018 (version 2)
- Version of Record updated: September 5, 2018 (version 3)
Copyright
© 2018, Kostaki et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,043
- Page views
-
- 407
- Downloads
-
- 23
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approach
eLife 7:e36709.
https://doi.org/10.7554/eLife.36709
Further reading
-
- Microbiology and Infectious Disease
A productive HIV-1 infection in humans is often established by transmission and propagation of a single transmitted/founder (T/F) virus, which then evolves into a complex mixture of variants during the lifetime of infection. An effective HIV-1 vaccine should elicit broad immune responses in order to block the entry of diverse T/F viruses. Currently, no such vaccine exists. An in-depth study of escape variants emerging under host immune pressure during very early stages of infection might provide insights into such a HIV-1 vaccine design. Here, in a rare longitudinal study involving HIV-1 infected individuals just days after infection in the absence of antiretroviral therapy, we discovered a remarkable genetic shift that resulted in near complete disappearance of the original T/F virus and appearance of a variant with H173Y mutation in the variable V2 domain of the HIV-1 envelope protein. This coincided with the disappearance of the first wave of strictly H173-specific antibodies and emergence of a second wave of Y173-specific antibodies with increased breadth. Structural analyses indicated conformational dynamism of the envelope protein which likely allowed selection of escape variants with a conformational switch in the V2 domain from an α-helix (H173) to a β-strand (Y173) and induction of broadly reactive antibody responses. This differential breadth due to a single mutational change was also recapitulated in a mouse model. Rationally designed combinatorial libraries containing 54 conformational variants of V2 domain around position 173 further demonstrated increased breadth of antibody responses elicited to diverse HIV-1 envelope proteins. These results offer new insights into designing broadly effective HIV-1 vaccines.
-
- Microbiology and Infectious Disease
For most retroviruses, including HIV, association with the plasma membrane (PM) promotes the assembly of immature particles, which occurs simultaneously with budding and maturation. In these viruses, maturation is initiated by oligomerization of polyprotein precursors. In contrast, several retroviruses, such as Mason-Pfizer monkey virus (M-PMV), assemble in the cytoplasm into immature particles that are transported across the PM. Therefore, protease activation and specific cleavage must not occur until the pre-assembled particle interacts with the PM. This interaction is triggered by a bipartite signal consisting of a cluster of basic residues in the matrix (MA) domain of Gag polyprotein and a myristoyl moiety N-terminally attached to MA. Here, we provide evidence that myristoyl exposure from the MA core and its insertion into the PM occurs in M-PMV. By a combination of experimental methods, we show that this results in a structural change at the C-terminus of MA allowing efficient cleavage of MA from the downstream region of Gag. This suggests that, in addition to the known effect of the myristoyl switch of HIV-1 MA on the multimerization state of Gag and particle assembly, the myristoyl switch may have a regulatory role in initiating sequential cleavage of M-PMV Gag in immature particles.
