Analysis after the abrupt increase in viral levels showed that the patient had become infected with a second strain of HIV, and two months later it was found that the two strains had exchanged portions of their Gag sequences initially targeted by his CTLs, allowing the virus to escape from that immune response. The patient's viral loads stabilized for a while but rose again several months later, when it was found that a second HIV mutation that more effectively evades control by HLA-B27 had developed, possibly in response to a second recombination of viral sequences.
"The first Gag recombination event facilitated escape from the primary immune response, shortly after which the immune response recovered to recognize this mutant strain," Streeck explains. "After the second recombination event and emergence of a more potent mutation, there was a dramatic reduction in the CTL response against both versions, leading to a significant increase in viral loads."
Todd Allen, PhD, of PARC-MGH, the study's senior author adds that, while recombination itself appears to be a random event, recombinant strains that are better able to evade the immune system are likely to become dominant through natural selection. He also stresses that even patients whose immune systems can partially control HIV should avoid a secondary infection that could lead to the development of an uncontrollable, recombinant viral strain.
Streeck notes, "Given the growing frequency of recombinant HIV strains worldwide, we need to better understand how immune system pressures may be driving their development and also determine how frequently patients exposed to a second strain of HIV become superinfected." He is a research fellow in Medicine at Harvard Medical School, where Allen is an associate professor of Medicine.
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| Contact: Sue McGreevey smcgreevey@partners.org 617-724-2764 Massachusetts General Hospital Source:Eurekalert |