Scheduled Seminars on 5/21/2013

Mileidy Gonzalez Delgado at 11:00  Edit  Reschedule  Delete

The founder virus in Human Immunodeficiency Virus (HIV) transmission seems not to be selected uniformly at random
HIV donor pools are known to contain largely heterogeneous viral populations. In contrast, HIV recipients feature a low diversity population tracing generally to only one or a few (at most) transmitted/founder virions from the donor pool. Thus, a long-standing question in the study of HIV has been whether founder viruses are chosen based on a selective advantage or whether they are chosen uniformly at random from the donor pool. To address this question, we combined statistical and computational methodologies to functionally characterize the env genes of donor and recipient subjects from one SIV animal trial and one HIV clinical breastfeeding trial. We used DNA-profile comparison to analyze (inoculum and mother) donor pools vs. (macaques and child) founder viruses against standard models of gp120 (a molecule mediating viral entry into the cell). Our results indicate that the founder viruses are statistically distinguishable from the viruses in the donor pools. To ensure that the observed differences in the donor-recipient pairs were not an artifact of data processing we checked for biases in the deduction of the founder viruses and in the construction of the gp120 models. Even when implementing 2 alternate methods of founder virus construction and 3 variations of gp120 modeling, the differences between the two groups remained statistically significant. Thus, we conclude that the gp120 molecules of SIV and HIV infecting virions seem to confer a selective advantage driving viral transmission. Our findings provide new knowledge regarding the molecular mechanisms of SIV and HIV transmission. Understanding the molecular mechanisms of SIV and HIV transmission, in turn, has the potential to inform the development of an effective HIV/AIDS vaccine as well as inform other prevention strategies (e.g. microbicides).

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