HIV Escape Mutations

Protection from CTL Recognition and Immune Response

Aug 26, 2007

Escape mutations can protect HIV-1 against detection by cytotoxic T-lymphocytes (CTL); however, some of these alterations in virus structure also provide a host advantage

CD8 T-cell responses are critical in containing HIV-1 replication and infection. During the acute phase of infection effective cytotoxic lymphocyte responses reduces virus levels in the host’s bloodstream reduce spread of the virus, slowing the progression of HIV infection to autoimmune deficiency syndrome (AIDS).

Mutation of key epitopes (minimum structural unit that can be recognized by a B or T cell receptor) allows the HIV-1 virus to evade host cytotoxic lymphocytes (CTL). These escape mutations impact the ability to mount effective CD8 T-cell response against HIV-1 epitopes during acute infection. Viral escape from CTL response due to mutation within the targeted epitope affect either the ability of the epitope to bind for presentation by the major histocompatibility complex (MHC) class I molecule on the cell surface, or alter the ability of the T-cell receptor (TCR) to recognize the MHC peptide complex.

CTL escape mutations are reportedly common and are selected by CTL responses restricted by a number of different HLA molecules. Mutations in regions within or flanking a target epitope can affect recognition of HIV-1 by CD8 T-cells. A single amino acid mutation in a key CTL recognition site can inhibit normal processing of the viral antigen by T-cells, and presentation of the mutated epitope by the major histocompatibility complex (MHC) on the cell surface. Meanwhile the same mutation in a second partially overlapping epitope can impair MHC-peptide-TCR (T-cell receptor) interaction affecting immune recognition of the altered epitope.

T-cell response can be affected by changes at any one of the steps in processing target epitopes.

Certain human leukocyte antigen (HLA) genotypes are associated with slower spread of HIV infection and long-term HIV control. For example, B57, B5801 and B27 human leukocyte antigen (HLA) alleles are associated with effective HIV control.

Horizontal transmission of HIV-1 strains capable of encoding antigen-processing mutations does occur. One of the escape mutations reported in individuals with human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801 reverts to wild-type (non-mutated virus) after transmission to individuals who do not have HLA-B57 or B5801 in their genotype. In contrast a second escape mutation in the epitope was maintained after transmission.

Reversion of HIV-1 to its non-mutated form following transmission depends on the impact that the mutation has on viral fitness or its ability to replicate. Transmitted mutations no longer required to evade host HLA-B57 or B5801 CD8 T-cell responses, or that negatively affects the structure or function of an HIV-1 protein, is likely to revert in the new host. HIV-1 must maintain a balance between escape and reversion in order to survive. The frequency of HLA alleles (e.g. B27, B57, B5801) that force mutations in HIV-1 epitopes targeted by cytotoxic lymphocytes, and the purifying process that results from HIV-1’s battle for balance will affect the spread and evolution of HIV-1 within the population.

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Source:

Allen TM, et al. Selection, Transmission, and Reversion of an Antigen-Processing Cytotoxic T-Lymphocyte Escape Mutation in Human Immunodeficiency Virus Type 1 Infection

The copyright of the article HIV Escape Mutations in Microbiology is owned by Judy Arbique. Permission to republish HIV Escape Mutations in print or online must be granted by the author in writing.