ArticleVirology2007
CD4 and MHC-I downregulation are conserved in primary HIV-1 Nef alleles from brain and lymphoid tissues, but Pak2 activation is highly variable.
Article in Virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Multifaceted Role of Nef in HIV-Associated Neurocognitive Disorder: Histopathological Alterations and Underlying Mechanisms.Brain sciences · 2025Review
- HIV-1 Balances the Fitness Costs and Benefits of Disrupting the Host Cell Actin Cytoskeleton Early after Mucosal Transmission.Cell host & microbe · 2019Article
- HIV-1 Latency and Eradication: Past, Present and Future.Current HIV research · 2016Review
- Explaining the determinants of first phase HIV decay dynamics through the effects of stage-dependent drug action.PLoS computational biology · 2013Article
- Mechanisms of HIV-1 Nef function and intracellular signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2011Review
- HIV-1 nef protein structures associated with brain infection and dementia pathogenesis.PloS one · 2011Article
- CD4 and MHC class 1 down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates.Journal of neurovirology · 2011Article
- Genetic and functional heterogeneity of CNS-derived tat alleles from patients with HIV-associated dementia.Journal of neurovirology · 2011Article
- Editorial neuroAIDS review.AIDS (London, England) · 2011Review
- Evidence for adaptive evolution at the divergence between lymphoid and brain HIV-1 nef genes.AIDS research and human retroviruses · 2010Article
- An emerging role for p21-activated kinases (Paks) in viral infections.Trends in cell biology · 2010Review
- At the crossroads of homoeostasis and disease: roles of the PACS proteins in membrane traffic and apoptosis.The Biochemical journal · 2009Review
- Functional characterization of the human immunodeficiency virus type 1 Nef acidic domain.Journal of virology · 2008Article
- HIV-1 Nef: at the crossroads.Retrovirology · 2008Review
- HIV-1 Nef binds PACS-2 to assemble a multikinase cascade that triggers major histocompatibility complex class I (MHC-I) down-regulation: analysis using short interfering RNA and knock-out mice.The Journal of biological chemistry · 2008Article
- Human immunodeficiency virus type 1 Nef recruits the guanine exchange factor Vav1 via an unexpected interface into plasma membrane microdomains for association with p21-activated kinase 2 activity.Journal of virology · 2008Article
- Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
HIV-1 compartmentalization in the CNS has been demonstrated for gag, pol, and env genes. However, little is known about tissue compartmentalization of nef genes and their functional characteristics in brain. We have cloned 97 nef genes and characterized 10 Nef proteins from autopsy brain and lymphoid tissues from 2 patients with AIDS and HIV-1-associated dementia. Distinct compartmentalization of brain versus lymphoid nef genes was demonstrated within each patient. CD4 and MHC-I downregulation were conserved in all tissue-derived Nefs. However, MHC-I downregulation by brain-derived Nefs was weaker than downregulation by lymphoid-derived Nefs. The motifs KEEE- or EKEE- at the PACS-1 binding site represented brain-specific signature patterns in these 2 patients and contributed to the reduced MHC-I downregulation activity of brain-derived Nefs from these patients. Pak2 association was highly variable in Nefs from both patients. Three of 10 tissue-derived Nefs coimmunoprecipitated activated Pak2, with strong association demonstrated for only 2 Nefs. The ability of Nef to associate with activated Pak2 did not correlate with brain or lymphoid tissue origin. Nef genes from viruses isolated from brain by coculture with PBMC were not closely related to sequences amplified directly from brain tissue, suggesting that viral selection or adaptation occurred during coculture. This study of tissue-derived HIV-1 Nefs demonstrates that CD4 and MHC-I downregulation are highly conserved Nef functions, while Pak2 association is variable in late stage AIDS patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.