Using nonhuman primates to model HIV transmission

Abstract

Purpose of Review One of the major obstacles in fully understanding HIV transmission comes from the impracticality of studying transmission in humans. Because of this encumbrance, the early phases of HIV transmission and systemic dissemination are poorly understood. In order to fully comprehend these critical steps in HIV infection, animal models must be devised to accurately reflect HIV’s mode of action. This review seeks to highlight the essential nature of modeling HIV transmission in nonhuman primates. Recent Findings Recently it was discovered that HIV infection is established in newly infected recipients by a single or few transmitted/founder variants. This has reshaped how animal modeling is conducted with researchers currently recapitulating a physiologically relevant, low-titer infection. Pertinent animal models have been established for the most common routes of infection, including rectal, vaginal, and penile transmission; models for intravenous and oral transmission are still in developmental stages. Summary These limited dose models now accurately reflect HIV transmission in humans, and provide a realistic experimental platform for vaccine development and other intervention strategies which can be used to inform vaccine development in humans. Using information obtained in NHP and human trials, it is conceivable to envision effective prevention modalities in the near future.

Factors Associated with Siman Immunodeficiency Virus Transmission in a Natural African Nonhuman Primate Host in the Wild

“…The high genetic diversity identified in these chronic samples confirmed our assumption that the association between seronegativity and high VLs is indeed due to recent infection. We therefore assessed in these samples the number of transmitted founder variants and showed that SIV transmission in the wild is characterized by the same bottleneck as the one described in progressive HIV/SIV infections (49,50,111).…”

“…As a result, in the vast majority of transmissions, infection is initiated by a single genetic unit (50). It is considered that this genetic bottleneck is due to either a very low infectious dose at the time of transmission, a significant host barrier to new infections, or both (49,50).…”

“…This bottleneck effect is currently explained by the low efficiency of virus penetration through mucosal layers and the potential selective pressure at the sites of transmission in either the donor or the recipient that could shape the transmitted viral strains (50). In addition to the route of transmission, cofactors, such as the presence of a sexually transmitted infection or the use of hormonal contraceptives, may affect the complexity of the transmitted virus population (49).…”

“…Thus, characterization of the genetic diversity of the HIV population during the early stages of infection, when the transmitted strains can be inferred after single-genome amplification (SGA), established that in most of the cases of heterosexual transmission infection is founded by a single strain from the donor viral population (45,48). In the case of intrarectal homosexual intercourse, more strains are transmitted, while in the case of transmission through intravenous drug use, which bypasses the mucosal bottleneck, multiple strains can be identified (49,50).…”

Molecularly Tagged Simian Immunodeficiency Virus SIVmac239 Synthetic Swarm for Tracking Independent Infection Events

“…Limiting-dose SIV challenges, which involve a reduction of the experimental viral inoculum size such that systemic infection is initiated by either one or only a few transmitted viral variants, have become a common and preferred method of modeling mucosal HIV infection in NHPs (1,(10)(11)(12)(13). This approach, which more closely recapitulates the inefficient nature of mucosal HIV transmission than traditional "high-dose" challenge models, requires the use of a virus stock containing sufficient sequence diversity to allow individual viral variants to be distinguished.…”