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Cited by 45HIV Research and TreatmentChromosomal and Genetic VariationsEvolution and Genetic Dynamics

Evidence for Restriction of Ancient Primate Gammaretroviruses by APOBEC3 but Not TRIM5α Proteins

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Perez-Caballero, David, Soll, Steven J., Bieniasz, Paul D.·2008·PLoS Pathogens
DOI 10.1371/journal.ppat.1000181PMC PMC2564838
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Abstract

Because of evolutionary pressures imposed through episodic colonization by retroviruses, many mammals express factors, such as TRIM5alpha and APOBEC3 proteins, that directly restrict retroviral replication. TRIM5 and APOBEC restriction factors are most often studied in the context of modern primate lentiviruses, but it is likely that ancient retroviruses imposed the selective pressure that is evident in primate TRIM5 and APOBEC3 genes. Moreover, these antiretroviral factors have been shown to act against a variety of retroviruses, including gammaretroviruses. Endogenous retroviruses can provide a 'fossil record' of extinct retroviruses and perhaps evidence of ancient TRIM5 and APOBEC3 antiviral activity. Here, we investigate whether TRIM5 and APOBEC3 proteins restricted the replication of two groups of gammaretroviruses that were endogenized in the past few million years. These endogenous retroviruses appear quite widespread in the genomes of old world primates but failed to colonize the human germline. Our analyses suggest that TRIM5alpha proteins did not pose a major barrier to the cross-species transmission of these two families of gammaretroviruses, and did not contribute to their extinction. However, we uncovered extensive evidence for inactivation of ancient gammaretroviruses through the action of APOBEC3 cytidine deaminases. Interestingly, the identities of the cytidine deaminases responsible for inactivation appear to have varied in both a virus and host species-dependent manner. Overall, sequence analyses and reconstitution of ancient retroviruses from remnants that have been preserved in the genomes of modern organisms offer the opportunity to probe and potentially explain the evolutionary history of host defenses against retroviruses.

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  • The finding that human TRIM5α binds a resurrected chimpanzee ERV capsid was not replicated in a separate study.

    “However, this finding was not replicated in a separate study 62.”

    From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [62]

    The Results and Discussion report that CERV1 capsid chimeras were not restricted by human TRIM5α, contrasting with an earlier study. They tested restriction, however, not whether human TRIM5α binds the capsid, so the specific binding finding is not shown to have failed replication. Page numbers are unavailable in our copy. (LLM, conf=0.86)

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Authors
Perez-Caballero, D., Soll, S. J., & Bieniasz, P. D.
Affiliations
Aaron Diamond AIDS Research Center (US)
Corresponding author
Bieniasz, Paul D.
ORCID
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2008-10-17
Volume
4
Issue
10
Pages
e1000181
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1000181
PMC
PMC2564838
OpenAlex
W2072662088
Cited by
45
References
53
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 10 · 2012: 5
FWCI
1.24
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R01 AI64003, R01AI064003)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords
gammaretrovirus, APOBEC3, TRIM5α, endogenous retroviruses, retroviral restriction factors, cytidine deaminase, primate lentiviruses, interspecies transmission, host-virus coevolution, Old World primates
MeSH terms
Animals, Pan troglodytes, Cytidine Deaminase, Humans, Macaca mulatta, Models, Molecular, Phylogeny, Primates, Proteins, Virus Replication, Gammaretrovirus, Evolution, Molecular, Endogenous Retroviruses, Capsid Proteins, NIH 3T3 Cells, Ubiquitin-Protein Ligases, Mice, Host-Pathogen Interactions

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