| Literature DB >> 30927712 |
Lisa Naidoo1, Zinhle Mzobe1, Steven W Jin2, Erasha Rajkoomar1, Tarylee Reddy3, Mark A Brockman4, Zabrina L Brumme5, Thumbi Ndung'u6, Jaclyn K Mann7.
Abstract
Functional characterisation of different HIV-1 subtypes may improve understanding of viral pathogenesis and spread. Here, we evaluated the ability of 345 unique HIV-1 Nef clones representing subtypes A, B, C and D to inhibit NFAT signalling following TCR stimulation. The contribution of this Nef function to disease progression was also assessed in 211 additional Nef clones isolated from unique subtype C infected individuals in early or chronic infection. On average, subtype A and C Nef clones exhibited significantly lower ability to inhibit TCR-mediated NFAT signalling compared to subtype B and D Nef clones. While this observation corroborates accumulating evidence supporting relative attenuation of subtypes A and C that may paradoxically contribute to their increased global prevalence and spread, no significant correlations between Nef-mediated NFAT inhibition activity and clinical markers of HIV-1 infection were observed, indicating that the relationship between Nef function and pathogenesis is complex.Entities:
Keywords: HIV-1 Nef; HIV-1 disease progression; HIV-1 subtype C; HLA-associated polymorphisms; Immune-driven escape mutations; NFAT inhibition; TCR signalling
Mesh：
Substances：
Year: 2019 PMID： 30927712 PMCID： PMC6526282 DOI： 10.1016/j.virol.2019.02.011
Source DB: PubMed Journal: Virology ISSN： 0042-6822 Impact factor: 3.616