HIV vaccine design should adapt as HIV virus mutates

BIRMINGHAM, Ala. – Human immunodeficiency virus is known to be a highly variable virus that adapts to a person’s immune response during the lifetime infection, and a new study published in Nature Medicine shows that viral adaptation in HIV can predict a person’s current disease status, as well as the degree to which newly transmitted HIV-1 is adapted to their new host.

By using a novel method to measure the extent of adaptation of a virus to a person’s cellular immune response, the investigators were able to predict how rapidly the disease will progress in that person.

The cellular arm of the immune response, through CD8+ T-cells, eliminates HIV-infected cells. These T-cells are activated by pieces of the virus, peptide epitopes, presented on the human leukocyte antigen proteins on the surface of antigen-presenting cells. HLA is a cell surface protein that is one of the most polymorphic variable parts of the human genome, as unique as each person’s DNA.

Some spontaneous mutations in HIV change the epitopes, the antigens to which a T-cell binds, so that the HLA proteins no longer present them effectively, and no longer stimulate an immune response. This process of viral adaptation is constantly occurring, and some adaptations persist even after sequential transmissions to new individuals.

An international team, led by scientists from Microsoft Research, the University of Alabama at Birmingham and Emory University, uses a model to quantify viral adaptation, showing that being infected by a virus highly adapted to their immune response is highly detrimental to that individual.

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