Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-2-2
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1538-2443
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
82-91
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
pubmed-meshheading:21165790-AIDS Dementia Complex, pubmed-meshheading:21165790-Alleles, pubmed-meshheading:21165790-Amino Acid Sequence, pubmed-meshheading:21165790-Antigens, CD4, pubmed-meshheading:21165790-Brain, pubmed-meshheading:21165790-Cell Line, pubmed-meshheading:21165790-Central Nervous System, pubmed-meshheading:21165790-Down-Regulation, pubmed-meshheading:21165790-Genes, MHC Class I, pubmed-meshheading:21165790-Genes, nef, pubmed-meshheading:21165790-HIV Infections, pubmed-meshheading:21165790-HIV-1, pubmed-meshheading:21165790-Humans, pubmed-meshheading:21165790-Lymphoid Tissue, pubmed-meshheading:21165790-Male, pubmed-meshheading:21165790-Molecular Sequence Data, pubmed-meshheading:21165790-Phylogeny, pubmed-meshheading:21165790-Virus Replication, pubmed-meshheading:21165790-nef Gene Products, Human Immunodeficiency Virus
pubmed:year
2011
pubmed:articleTitle
CD4 and MHC class 1 down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates.
pubmed:affiliation
Center for Virology, Burnet Institute, 85 Commercial Rd, Melbourne, 3004 VIC, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural