Yet another way HIV fools the immune system uncovered

Washington, July 22 : Scientists at the Partners AIDS Research Center at Massachusetts General Hospital (PARC/MGH) have revealed another mechanism whereby HIV fools the immune system.

According to them, when any HIV patient become infected with a second strain of the virus, the two viral strains can exchange genetic information to create a third, recombinant strain of the virus.

The presence of multiple viral strains, scientifically known as superinfection, frequently causes a loss of immune control of viral levels, they say.

The researchers say that how and where viral strains swap DNA may be determined by the immune response against the original infecting strain.

"The implication that recombination events are selected by immune responses identifies a new mechanism for the virus to escape the patient's immune system, which would present additional challenges to vaccine design," says Dr. Hendrik Streeck, of PARC/MGH, one of the lead authors of the study paper.

"This finding also has worldwide implications for the development of more complex strains of HIV," the researcher adds.

During the study, the researchers carried out an examination of blood samples from an individual who was known to have a powerfully protective Class I allele called HLA-B27, but began to experience rapid increases in viral levels much sooner than would have been expected.

The researchers found that his immune response against HIV had predictably controlled the virus for about a year and a half after he was first diagnosed.

The effective immune response was primarily directed against a short segment of the Gag protein typically targeted in HLA-B27 patients.

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 evade the 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. 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," Streeck says.

According to senior author of the study Dr. Todd Allen, 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.

"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 notes.

Their report will appear in the Journal of Experimental Medicine and has been released online.

ANI