Transcription of Preintegrated HIV-1 cDNA Modulates Cell Surface Expression of Major Histocompatibility Complex Class I via Nef

Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells

“…The first relates to immunoevasion mediated by HIV Nef, which acts to downregulate MHC-I on infected cells, thereby diminishing recognition by CD8 + T cells (61). In productive HIV replication, Nef immunoevasion is likely limited -to some extent -by the early presentation of antigen from incoming virions prior to Nef-mediated MHC-I downregulation (within 2-6 hours of infection) (62)(63)(64)(65)(66)(67)(68)(69)(70). In the setting of reactivation from latency there is no parallel to this eclipse phase, and the expression of late gene products (such as Gag) will occur only after MHC-I downregulation occurs.…”

The Dual Role of Pharmacogenetics in HIV Treatment: Mutations and Polymorphisms Regulating Antiretroviral Drug Resistance and Disposition

“…However, such intermediates are detected in circular or linear isoforms in the nucleus as well as the cytoplasm (Wu, 2004). Although unintegrated viral DNA has been shown to mediate expression of viral regulatory proteins and to cause the depletion of major histocompatibility complex and viral receptors, the infectivity of such intermediates is still debatable (Wu, 2004;Sloan et al, 2010Sloan et al, , 2011.…”

Human immunodeficiency virus type 1 Vpu and cellular TASK proteins suppress transcription of unintegrated HIV-1 DNA

“…When HIV-1 integration is blocked CD4, CCR5 and CXCR4 are down regulated by Nef, leading to a restriction of superinfection events [57-60]. In addition, HLA molecules recognized by helper [61] and cytotoxic T-cells are down regulated by Nef while HLA molecules that are recognized by natural killer cells are not affected by Nef [62-65]. Therefore early production of Nef from uDNA may be important for immune evasion by HIV-1 [61].…”