HIV-2 evades restriction by ZAP through adaptations in the U3 LTR region despite increased CpG levels Article Swipe
Dorota Kmieć
,
Rayhane Nchioua
,
Alexander Gabel
,
Asimenia Vlachou
,
Sabina Ganskih
,
Sümeyye Erdemci-Evin
,
Stacey A. Lapp
,
Diane G. Carnathan
,
Steven E. Bosinger
,
Ben Berkhout
,
Atze T. Das
,
Mathias Munschauer
,
Frank Kirchhoff
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gkaf826
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gkaf826
Simian immunodeficiency viruses infecting sooty mangabeys (SIVsmm) gave rise to nine groups of human immunodeficiency virus type 2 (HIV-2). Two of these (A and B) spread substantially with an estimated 1–2 million individuals affected. The evolutionary adaptations that facilitated HIV-2’s spread in humans are still poorly understood. Here, we report that diverse SIVsmm strains efficiently infect primary human T cells. However, they are more sensitive to interferon than HIV-2, indicating that interferon-stimulated genes (ISGs) pose a barrier to the successful spread of SIVsmm in humans. One of the best-known antiviral ISGs is the zinc finger antiviral protein (ZAP), which targets CpG dinucleotides in RNA. To evade ZAP-mediated restriction, many viruses, including HIV-1, suppress their CpG content. Unexpectedly, we found that HIV-2 is more resistant to ZAP restriction than HIV-1 and SIVsmm despite having 33% more CpGs. Identification of ZAP-binding sites using RNA enhanced crosslinking immunoprecipitation and analyses of chimeric HIV-2/SIVsmm viruses revealed that the determinants of ZAP resistance map to the nef/U3 region and promote HIV-2 replication in primary human T cells. Our results indicate that HIV-2 evolved a CpG-independent ZAP resistance mechanism which might have been facilitated by relaxed functional constraints acting on Nef in the human host.
Related Topics
Concepts
Biology
CpG site
Genetics
Human immunodeficiency virus (HIV)
DNA methylation
Gene
Virology
Gene expression
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/nar/gkaf826
- https://academic.oup.com/nar/article-pdf/53/16/gkaf826/64166697/gkaf826.pdf
- OA Status
- gold
- References
- 104
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4413843669
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4413843669Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/nar/gkaf826Digital Object Identifier
- Title
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HIV-2 evades restriction by ZAP through adaptations in the U3 LTR region despite increased CpG levelsWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-08-07Full publication date if available
- Authors
-
Dorota Kmieć, Rayhane Nchioua, Alexander Gabel, Asimenia Vlachou, Sabina Ganskih, Sümeyye Erdemci-Evin, Stacey A. Lapp, Diane G. Carnathan, Steven E. Bosinger, Ben Berkhout, Atze T. Das, Mathias Munschauer, Frank KirchhoffList of authors in order
- Landing page
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https://doi.org/10.1093/nar/gkaf826Publisher landing page
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https://academic.oup.com/nar/article-pdf/53/16/gkaf826/64166697/gkaf826.pdfDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://academic.oup.com/nar/article-pdf/53/16/gkaf826/64166697/gkaf826.pdfDirect OA link when available
- Concepts
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Biology, CpG site, Genetics, Human immunodeficiency virus (HIV), DNA methylation, Gene, Virology, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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104Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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