Multiple mechanisms exist by which HIV evades specific immune responses. These escape strategies are mutational or constitutive, and result in the evasion of cellular and antibody responses. (Sewell et al., 2000)
HIV-specific CTLs kill HIV-infected cells following recognition of viral peptides presented in association with MHC-I molecules on the surface of virally infected cells. Epitope deletion in HIV envelope, secondary to viral mutation, occurs in primary infection and later stages of HIV disease, and results in the loss of antigen recognition by HIV-specific CTLs (Goulder et al., 1997; Price et al., 1997; Goulder et al., 2001) Multiple lines of evidence suggest that mutational escape plays an important role in HIV disease pathogenesis. Viral mutants which have escaped HIV-specific CTLs are more frequently found in mothers who transmit HIV to their infants than in non-transmitting mothers. (Wilson et al., 1999) Furthermore, following autologous transfusion of HIV-specific CTL clones directed at a single HIV epitope, viral mutants evolve that lack the targeted epitope and thus escape control of the transfused HIV-specific CTLs. (Koenig et al., 1995) Viral escape from HIV-specific CTLs is associated with a poorer clinical outcome.(Koenig et al., 1995) At the population level, escape from CTL determines the distribution of viral sequences so that the predominant sequences are those that have escaped from the predominant HLA alleles in the population.(Moore et al., 2002) HIV escape from antibody responses has also been demonstrated, but is less well studied than escape from HIV-specific cytotoxic T cells. Emergence of viral mutants which resist neutralisation by autologous HIV-specific antibodies has been demonstrated in people with symptomatic primary infection.(Albert et al., 1990)
Neutralising antibodies have been found in some people with long- term slowly progressive HIV disease,(Pilgrim et al., 1997) but these antibodies lose their capacity to neutralise HIV over time. Serum fails to neutralise concurrent viral isolates present in people with long-term infection, despite neutralisation of earlier isolates. Broadly neutralising antibodies are now considered to be the result of viral escape from neutralising antibodies.(Wibmer et al., 2013) These observation suggest viral isolates continually evolve to resist the humoral immune response. (Bradney et al., 1999)
HIV has developed other means to evade HIV-specific immune responses. First, post-integration viral latency protects the infected cell from immune surveillance, as viral antigens are not expressed on the cell surface. These latently infected cells produce infectious HIV following subsequent cellular activation. Second, a number of HIV proteins interfere with critical cellular processes that facilitate the host immune response. Specifically, the HIV tat protein impairs antigen processing by interfering with proteasome function and downregulating MHC-II molecule expression while the HIV Nef protein downregulates the expression of CD4 and MHC-I molecules.(Kanazawa et al., 2000; Schwartz et al., 1996; Seeger et al., 1997; Piguet et al., 1998) Finally, HIV proteins, specifically Nef, induce apoptosis of HIV- specific CTLs by increasing the expression of FasL, resulting in apoptosis of Fas-expressing CTLs. This process is referred to as back-killing (Geleziunas et al., 2001).