Link between Primate Lentiviral Coreceptor Usage and Nef Function
| Autor: | Guido Silvestri, Donald L. Sodora, Hangxing Yu, Hui Li, Asma Shabir, Matthias Geyer, Frank Kirchhoff, Beatrice H. Hahn, Jan Schmökel |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
CD4-Positive T-Lymphocytes
Receptors CXCR4 CD3 Complex Receptors CCR5 Cercocebus CD3 viruses Molecular Sequence Data Simian Acquired Immunodeficiency Syndrome Antigen-Presenting Cells HIV Infections medicine.disease_cause Lymphocyte Activation CXCR4 General Biochemistry Genetics and Molecular Biology Gene Products nef Article 03 medical and health sciences biology.animal medicine Animals Primate Lymphocyte Count Antigen-presenting cell lcsh:QH301-705.5 Immunodeficiency Cells Cultured 030304 developmental biology 0303 health sciences biology 030302 biochemistry & molecular biology Gene Products env virus diseases Simian immunodeficiency virus medicine.disease Virology 3. Good health Protein Structure Tertiary Viral replication lcsh:Biology (General) Receptor-CD3 Complex Antigen T-Cell Immunology HIV-2 biology.protein HIV-1 Simian Immunodeficiency Virus Immunologic Memory Function (biology) |
| Zdroj: | Cell reports Cell Reports Cell Reports, Vol 5, Iss 4, Pp 997-1009 (2013) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2013.10.028 |
| Popis: | Summary Simian immunodeficiency virus (SIVsmm) infection of sooty mangabeys ( Cercocebus atys ) is characterized by stable CD4 + T cell counts despite high plasma levels of CCR5-tropic viruses. However, in rare instances, SIVsmm acquires CXCR4 coreceptor tropism and causes severe CD4 + T cell depletion, albeit without clinical signs of immunodeficiency. Here, we show that CXCR4-tropic SIVsmm strains lost their ability to downmodulate TCR-CD3 by evolving unusual Nef mutations that initially reduced (I132V) and subsequently disrupted (I123L and L146F) interaction with the CD3 ζ chain. This coevolution of Env and Nef function suggests that CD3 downmodulation is advantageous for viral replication in activated CCR5 + memory T cells, but not in resting naive CXCR4 + T cells that have not yet undergone TCR-CD3-mediated stimulation. This may explain why HIV-1, which generally lacks the CD3 downmodulation function, commonly switches to CXCR4 usage, whereas this is extremely rare for SIV strains that have retained this Nef activity. |
| Databáze: | OpenAIRE |
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