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Cited by 84HIV Research and TreatmentT-cell and Retrovirus StudiesXenotransplantation and immune response

Retroviral infection in vivo requires an immune escape virulence factor encrypted in the envelope protein of oncoretroviruses

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Schlecht-Louf, Géraldine, Renard, Martial, Mangeney, Marianne, Letzelter, Claire, Richaud, Aurélien, Ducos, Bertrand, Bouallaga, Isabelle, Heidmann, Thierry·2010·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0913122107PMC PMC2840525
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Abstract

We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins (Envs). The envelope-mediated immunosuppression was manifested by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation specifically abolishes IS activity without affecting the “mechanical” fusogenic function of the entire envelope. Here, we genetically “switched off’ the envelope-mediated immunosuppression of an infectious retrovirus, the Friend murine leukemia virus, while preserving mutant envelope infectivity both ex vivo and in vivo, thus allowing us to test the functional importance of envelope-mediated immunosuppression in retrovirus physiology. Remarkably, we show, in vivo, that the non-IS mutant virus displays the same propagation kinetics as its WT counterpart in irradiated immunocompromised mice but that it is rapidly and totally cleared from normal immunocompetent mice, which become fully protected against a challenge with the WT retrovirus. Using cell depletion strategies, we further establish that envelope-mediated immunosuppression enables the retrovirus to escape innate (natural killer cells) and adaptive (CD8 T cells) antiviral effectors. Finally, we show that inactivated mutant virions induce higher humoral and cellular responses than their WT counterparts. In conclusion, our work demonstrates the critical role of Env-induced immunosuppression for retrovirus propagation in vivo and identifies a unique definite target for antiretroviral therapies and vaccine strategies, also characterized in the human T-cell leukemia virus (HTLV) and xenotropic murine leukemia virus-related virus (XMRV) retroviruses, opening unprecedented prospects for the treatment of retroviral diseases.

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Crossref · 10.1073/pnas.0913122107

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  • Immune suppression by the ISD appears necessary for efficient retroviral spread at least in mouse models.

    “Immune suppression by the ISD appears necessary for efficient retroviral spread at least in mouse models 50.”

    From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [50]

  • An immunosuppressive domain (ISD) has been identified within the transmembrane subunit of the envelope protein of Moloney MLV and Feline leukemia virus (FeLV).

    “A particular domain, termed immunosuppressive domain (ISD), has been identified within the transmembrane subunit of the envelope protein of Moloney MLV and Feline leukemia virus (FeLV)”

    From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [50]

  • The ISD is relatively conserved among many different retroviruses of other species, including human.

    “and was also shown to be relatively conserved among many different retroviruses of other species, including human 50,51.”

    From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [50]

  • Exogenous present-day retroviruses encode an envelope protein that exerts potent immunosuppression.

    “Exogenous present-day retroviruses encode an envelope protein that has been demonstrated to exert potent immunosuppression 50.”

    From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [50]

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Authors
Schlecht-Louf, G., Renard, M., Mangeney, M., Letzelter, C., Richaud, A., Ducos, B., Bouallaga, I., & Heidmann, T.
Affiliations
  • Unité des Rétrovirus Endogènes et Éléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8122 Institut Gustave Roussy, 94805 Villejuif, and Université Paris-Sud, 91405 Orsay, France; and
  • Université Paris-Sud (FR)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2010-02-23
Volume
107
Issue
8
Pages
3782-3787
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0913122107
PMC
PMC2840525
OpenAlex
W1992649987
Cited by
84
References
33
Citations by year
2026: 3 · 2025: 5 · 2024: 2 · 2023: 4 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 8 · 2016: 8 · 2015: 4 · 2014: 4 · 2013: 10 · 2012: 6
FWCI
3.72
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Centre National de la Recherche Scientifique
  • Institut Gustave-Roussy
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
Keywords
retroviral envelope protein, immune evasion, Friend murine leukemia virus, natural killer cells, CD8+ T cells, viral clearance, vaccination strategies, HTLV, XMRV
MeSH terms
Animals, Friend murine leukemia virus, Immune Tolerance, Leukemia, Experimental, Mice, Inbred BALB C, Mice, Inbred C57BL, Mutation, Retroviridae Infections, T-Lymphocytes, Cytotoxic, Tumor Virus Infections, Viral Envelope Proteins, Viral Vaccines, Virulence Factors, NIH 3T3 Cells, Mice

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