Researchers at the University of Oxford have discovered that HIV's ability to mutate in order to hide from the body's immune system also impairs its ability to replicate.
According to them, when HIV infects a cell, a complex of human immune proteins called HLA (short for human leukocyte antigen) alert killer T cells by displaying bits of the virus on the surface of the cell, in response to which the T-cells trigger immune attack.
AdvertisementThey suggest that individuals who have certain types of HLA proteins control infection better than others.
For instance, in people with HLA-B*5703, the virus multiplies less than in people with some other HLA variants likely because killer T cells in these individuals are quick to attack infected cells. However, HIV is tricky.
To get around HLA-B*5703, the virus mutates three amino acids that T cells need to recognize the infected cells, causing the killers to pass by the infected cell unnoticed.
Thus by mutating, the virus becomes invisible to the immune system.
In the new study, lead researcher Hayley Crawford showed that the triple mutant replicated 20 times slower than normal in cell culture.
During the study, the researchers examined Zambian couples in which one HLA-B*5703-expressing person infected with triple-mutant virus passed the infection to a partner who either did or didn't have the same HLA variant.
When transmitted to a person without HLAB*5703, the virus changed its mutated amino acids back to their original sequence because the benefit of avoiding killer T cells no longer outweighed the cost of reduced replication.
However, when transmitted to another HLA-B*5703-expressing person, the triple-mutated virus came out on top despite its reduced replication. In these individuals, the avoidance of killer T cells allowed the infection to rapidly proceed to clinical illness.
The study has been published in Journal of Experimental Medicine.
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