CD4 and MHC class 1 down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates

Gray, L, Gabuzda, D, Cowley, D, Ellett, A, Chiavaroli, L, Wesselingh, S, Churchill, M and Gorry, P 2011, 'CD4 and MHC class 1 down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates', Journal of NeuroVirology, vol. 17, no. 1, pp. 82-91.


Document type: Journal Article
Collection: Journal Articles

Title CD4 and MHC class 1 down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates
Author(s) Gray, L
Gabuzda, D
Cowley, D
Ellett, A
Chiavaroli, L
Wesselingh, S
Churchill, M
Gorry, P
Year 2011
Journal name Journal of NeuroVirology
Volume number 17
Issue number 1
Start page 82
End page 91
Total pages 10
Publisher Springer
Abstract Human immunodeficiency virus type 1 (HIV-1) nef undergoes adaptive evolution in the central nervous system (CNS), reflecting altered requirements for HIV-1 replication in macrophages/microglia and brain-specific immune selection pressures. The role of Nef in HIV-1 neurotropism and pathogenesis of HIV-associated dementia (HAD) is unclear. In this study, we characterized 82 nef alleles cloned from brain, cerebral spinal fluid, spinal cord, and blood/lymphoid tissue-derived HIV-1 isolates from seven subjects with HAD. CNS isolate-derived nef alleles were genetically compartmentalized and had reduced sequence diversity compared to those from lymphoid tissue isolates. Defective nef alleles predominated in a brain-derived isolate from one of the seven subjects (MACS2-br). The ability of Nef to down-modulate CD4 and MHC class 1 (MHC-1) was generally conserved among nef alleles from both CNS and lymphoid tissues. However, the potency of CD4 and MHC-1 down-modulation was variable, which was associated with sequence alterations known to influence these Nef functions. These results suggest that CD4 and MHC-1 down-modulations are highly conserved functions among nef alleles from CNS- and lymphoid tissue-derived HIV-1 isolates that may contribute to viral replication and escape from immune surveillance in the CNS.
Subject Medical Virology
Keyword(s) HIV-1
Dementia
Nef
Neurotropism
CNS
Lymphoid
CD4
MHC-1
DOI - identifier 10.1007/s13365-010-0001-6
Copyright notice © 2010 Journal of NeuroVirology, Inc. 2010
ISSN 1355-0284
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