Researchers note in vitro studies may not replicate results in vivo, potentially leading to erroneous conclusions
The major receptor for HIV entry into a cell—along with CD4—is known as CCR5. The CCR5 protein has been in the news of late due to its role enabling the remission of the “London patient” after a bone marrow transplant using cells from a donor with nonfunctioning CCR5 protein. The “Berlin patient” remains the only person known to have been cured of HIV following a similar transplant procedure more than ten years ago.
In a recent study published in the Journal of Virology, amfAR-funded scientist Dr. Sharon Lewin of Monash University in Melbourne, Australia, looked at CCR5 in a different way. Recognizing that sexual transmission of HIV occurs primarily through infection of CCR5-bearing T cells in the presence of semen, Lewin and colleagues explored the impact of semen on the amount of CCR5 present on T cells.
They found that in the test tube, seminal plasma—the fluid component of semen—from HIV-negative donors resulted in decreased amounts of CCR5 on those HIV target cells, making them potentially less susceptible to HIV infection. But when they exposed monkeys to seminal plasma they found that it often led to an increase—not a decline—in the number of CCR5-bearing HIV target cells present in the tissues.
The authors drew an important conclusion from their work: Test tube studies cannot reliably replicate the conditions under which immune cells may be attracted to genital mucosa in monkeys—and presumably in humans—leading to potentially erroneous conclusions.
These observations also have implications for certain types of contraceptives, such as condoms to block semen exposure, and the need for research on other types of contraceptives that might alter co-receptor expression.
Investigators for the ECHO Study—a clinical trial comparing three highly effective, reversible methods of contraception to evaluate potential links to increased risk of acquiring HIV—will present their findings at the 10th IAS Conference on HIV Science in July in Mexico City.
Dr. Laurence is amfAR’s senior scientific consultant.