Primary Human Immunodeficiency Virus Type 1 Nef Alleles Show Major Differences in Pathogenicity in Transgenic Mice

Abstract

We previously reported that the human immunodeficiency virus type 1 NL4-3 Nef is necessary and sufficient to induce a severe AIDS-like disease in transgenic (Tg)

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

“…In particular, the association of Nef with PAK has been studied in more detail, demonstrating that PAK2 is the preferred PAK isoform that associates with Nef (5,19,54). The interaction of Nef with PAK2 activity is conserved for many Nef proteins derived from HIV-1, HIV-2, and SIV strains (50,51,60) and is readily detectable in HIV-1-infected T lymphocytes as well as HIV-1 provirus transgenic mice (59,75). Many Nef alleles also aug-ment overall cellular PAK2 activity, but PAK2 activation is less well conserved and dispensable for the association of Nef with PAK2 activity (51).…”

HIV Nef Expression Favors the Relative Preservation of CD4+ T Regulatory Cells That Retain Some Important Suppressive Functions

“…In addition, our data showing that Nef is sufficient to affect Treg suggest that infection with viruses harboring different Nef alleles may account for some of these variations. Nef is polymorphic, and its alleles have been shown to exhibit remarkable variations in their functions (41), including when expressed in Tg mice (42).…”

Selective Expression of Human Immunodeficiency Virus Nef in Specific Immune Cell Populations of Transgenic Mice Is Associated with Distinct AIDS-Like Phenotypes

“…The ratio of HIV-specific 8.8-kb signal relative to the 18S ribosome-specific signal was obtained. In addition, transgene RNA expression was estimated by real-time quantitative reverse transcription-PCR (RT-PCR), as described previously (78,106). Tg Nef protein expression was assessed by Western blot analysis of lymphoid organs or purified cells from mice of different founder (F) lines, using rabbit anti-Nef antibody, as described previously (78,103).…”

“…In addition, transgene RNA expression was estimated by real-time quantitative reverse transcription-PCR (RT-PCR), as described previously (78,106). Tg Nef protein expression was assessed by Western blot analysis of lymphoid organs or purified cells from mice of different founder (F) lines, using rabbit anti-Nef antibody, as described previously (78,103). Proteins were visualized by incubating the membranes with secondary anti-rabbit antibodies coupled to Alexa 680 fluorochrome, followed by scanning with Odyssey infrared imaging system (Licor).…”

“…Statistical analyses (analysis of variance, Sigmastat, and the Student t test) were performed as previously described (26,78,106).…”