HIV pays a price for
invisibility
HIV
budding (green dots)
Mutations that help HIV hide from
the immune system undermine the virus's ability to replicate, show
an international team of researchers in the April 13 issue of the
Journal of Experimental Medicine. The study was published online on
March 23.
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. The T
cells recognize these HIV fragments and mobilize an attack.
Individuals who have certain types of HLA proteins control
infection better than others. In people with HLA-B*5703, for
example, 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. But 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 report, Hayley Crawford at the University of Oxford and
colleagues show that the virus pays a price for its invisibility.
The triple mutant replicated 20 times slower than normal in cell
culture.
The researchers went on to study 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, most likely 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. This
study suggests that vaccines should be designed to produce a T cell
response against a number of different viral peptides – something
that experimental human vaccines so far have yet to achieve.
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Rockefeller University Press. Thanks to Rockefeller University
Press for this article.