Having studied HIV-infected people with a particular gene, scientists have gained fresh insights into how the virus mutates and evolves in response to the body's immune pressure.
Dr. Eric Hunter of the Emory Vaccine Center and Oxford University graduate student Hayley Crawford studied people in Zambia and South Africa with one form of the HLA gene that helps the immune system control HIV, called HLA-B*5703.
AdvertisementHLA genes encode molecules that display fragments of viral proteins, known as epitopes, on the surface of infected cells.
When white blood cells known as cytotoxic T lymphocytes (CTLs) spot certain combinations of HLA molecules and viral epitopes, they attack the infected cells.
During the study, the researchers observed that a set of three mutations in HIV's Gag protein, which makes up the viral core, progressively slow viral replication.
They say that a triple-mutant virus replicates 20 times slower than normal in cell culture.
However, the same mutations effectively eliminate the ability of CTLs to detect the virus, so that in an infected person, once all three mutations are in place, viral abundance shoots upwards.
"In this situation, HIV resembles a thief pic king a lock. Once all three mutations are in place, the lock is picked and the virus can thrive because the immune system can't fight against it," Hunter says.
The Emory/Oxford researchers followed the mutations' fate after transmission by studying couples in which one person had infected the other.
They observed that the virus lost the mutations when the recipient lacked HLA-B*5703, as the three handicapping mutations were not useful in evading the new, different immune system.
However, unlucky recipients with the HLA gene, who got the triple-mutant virus from their partners, quickly got sick.
The results demonstrate the importance of CTLs, the white blood cells that attack viral infected cells, in controlling HIV infection.
They also suggest that a successful vaccine will need to induce responses to many epitopes, or combinations of HLA molecule and viral protein.
The study has been published in the Journal of Experimental Medicine.
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