Even though a number of animal models have been developed over the last three decades to study aspects of HIV infection, pathogenesis and control, none of the models had managed to replicate the physiological environment of the most common route of HIV transmission worldwide, vaginal intercourse.
Now researchers led by Mary Jane Potash at St Luke's-Roosevelt Hospital Center and New York's Columbia University Medical Center have come up with a new approach for modeling heterosexual transmission of HIV in vivo, a new study published in the journal Disease Models & Mechanisms reveals.
The work stems from an earlier collaboration between Potash and David J. Volsky (also from Columbia University); they established a chimeric HIV clone with a genetic modification that allows the virus to propagate in rodents instead of humans. Infection of mice with these viruses has been successfully applied to study aspects of HIV neuropathogenesis and to evaluate antiretroviral drugs and potential HIV vaccines. In their latest study, Potash and colleagues describe the efficient and reproducible transmission of chimeric HIV from infected male mice to uninfected females via mating, providing the first report of HIV transmission by coitus in an animal model. Treatment of females with antiretroviral drugs prior to mating prevented transmission of the virus, in line with observations in humans. Intriguingly, the efficiency of viral transmission declined during estrus in mice, providing evidence that the hormonal environment in the female reproductive tract can impact on host susceptibility to HIV infection. This finding has implications for HIV infection in humans, where it has been suggested that vulnerability to viral infection could vary during the menstrual cycle.
The model described here has several advantages compared with previous experimental approaches for investigating sexual transmission of HIV. For example, transmission occurs during mating, in contrast with earlier systems in which viral stocks need to be applied manually to the vaginal surface; thus, the system preserves features of the male and female reproductive tracts. This is important, as previous work has shown that host factors and cells in the seminal fluid activate cells in the female reproductive tract and enhance HIV infection, yet the underlying mechanisms remain poorly understood. Similarly, as indicated in this study, the local environment in the female reproductive tract can influence the rate and efficiency of HIV sexual transmission. By preserving the physiological features of coitus, the approach allows the dynamic aspects of viral sexual transmission to be investigated in vivo. Furthermore, the system can be used to investigate the efficacy of new interventive strategies aimed at preventing the most frequent route of HIV transmission.
"We developed this system to study HIV spread by mating in mice with the hope that it can be applied to promote practical approaches to prevent HIV sexual transmission to people at risk" explained Dr Potash, when asked about the goals of this research.
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