Key Points
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HIV escapes the immune system by hiding inside cells. In resting cells, blocks to the initiation and elongation of viral transcription have been proposed.
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Viral regulatory and accessory proteins contribute to immune escape.
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The transcriptional transactivator Tat can inhibit antigen processing and presentation by MHC class I and class II molecules.
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The viral 'negative effector' Nef can block the expression of MHC class I molecules, as well as trigger the apoptosis of effector T cells through interactions between FAS ligand and FAS.
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The anti-apoptotic effects of Nef could contribute to the survival of infected cells.
Abstract
Viruses that induce chronic infections can evade immune responses. HIV is a prototype of this class of pathogen. Not only does it mutate rapidly and make its surface components difficult to access by neutralizing antibodies, but it also creates cellular hideouts, establishes proviral latency, removes cell-surface receptors and destroys immune effectors to escape eradication. A better understanding of these strategies might lead to new approaches in the fight against AIDS.
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Acknowledgements
We thank members of our laboratories for helpful discussions, and G. Thomas for communicating unpublished results. This work was supported by grants from the National Institutes of Health, the Nora Eccles Treadwell Foundation and the Universitywide AIDS Research Program (to B.M.P.), and the Swiss National Science Foundation and the National Centre for Competence in Research 'Frontiers in Genetics' (to D.T.).
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Authors and Affiliations
Glossary
- MICROGLIAL CELLS
-
Resident brain macrophages. Bone-marrow-derived cells that express CD4 and chemokine receptors
- PRE-INTEGRATION COMPLEX
-
A large complex of viral complementary DNA, integrase (IN) protein, matrix (MA) protein, reverse transcriptase (RT), viral protein r (Vpr) and host proteins that is docked at the nuclear envelope. The viral genome then crosses the nucleopore, together with an as-yet-undefined set of these proteins, before integrating into host chromosomes.
- TATA BOX
-
A highly conserved DNA sequence (consensus TATAA) that is found in the promoter of many (mainly rapidly transcribed) cellular and viral genes, 25–35 bases upstream of the RNA start site.
- POSITIVE TRANSCRIPTION ELONGATION FACTOR B
-
(P-TEFb). This complex consists of the carboxy-terminal domain kinase CDK9 and the C-type cyclin CYCT1, CYCT2a, CYCT2b or CYCK. It is required for the elongation of transcription.
- NEGATIVE TRANSCRIPTION ELONGATION FACTOR
-
(N-TEF). This complex consists most probably of 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB)-sensitivity-inducing factor (DSIF) and negative elongation factor (NELF); the subunit containing arginine–glutamate repeats (RD) binds TAR.
- PRE-INITIATION COMPLEX
-
The transcription complex that is recruited to promoters through activators, consisting of RNA polymerase II and mediators that bind its unphosphorylated carboxy-terminal domain.
- CRM1/RANGTP COMPLEX
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A complex that transports proteins containing a nuclear-export signal from the nucleus to the cytoplasm. The cargo is released in the cytoplasm after the hydrolysis of GTP to GDP.
- CLATHRIN-COATED PITS
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Subdomains of the plasma or endosomal membranes that are involved in endocytosis.
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Peterlin, B., Trono, D. Hide, shield and strike back: how HIV-infected cells avoid immune eradication. Nat Rev Immunol 3, 97–107 (2003). https://doi.org/10.1038/nri998
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DOI: https://doi.org/10.1038/nri998
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