New animal model recapitulates sexual HIV transmission

Most HIV transmissions happen heterosexually, but so far, animal models don’t accurately recapitulate this process. Instead, researchers manually place a droplet of a solution that contains viruses inside the vagina of females. 

Now, researchers have for the first time modeled heterosexual HIV transmission in a much more accurate way: In mice that actually have sex (Dis. Model. & Mech., 2013; doi: 10.1242/dmm.012617).

Because HIV doesn’t normally infect mice, they have made a version of HIV that has all HIV genes except that HIV Env is replaced with the Envelope protein from murine leukemia virus. This results in a “chimeric HIV” that, like HIV, can infect CD4+ T cells and macrophages and replicate in normal laboratory mice.

When the researchers placed male mice infected with this virus with uninfected females, they found that most of the female mice became infected after seven or fewer nights of mating. Treatment with the antiretroviral tenofovir or ddC largely prevented this transmission, and female mice that were at a certain stage in their reproductive cycle where their estrogen levels are highest (called estrus), were less likely to get infected.

The model, the researchers say, will make it possible to model HIV transmission more realistically. For example, it can take into account effects of the male seminal fluid or the female reproductive cycle on HIV transmission. It can also model the effect of unprotected sex on the induction of an inflammatory process in the female reproductive tract that has recently been reported in humans and might result in induction of additional HIV target cells, says lead author Mary Jane Potash from St. Luke’s Roosevelt Hospital Center and Columbia University in New York.

Because of the lack of HIV Env, the model is less suited for studies of vaccines that are expected to work by inducing neutralizing antibodies specific for HIV Env; however, HIV candidate vaccines that induce cellular immune responses have already been successfully tested, says Potash.