By Matthew Lee ‘21
Ever since it made a global impact in the 1980s, HIV has increasingly become one of the world’s most studied diseases. However, the exact mechanisms that underlie vertical HIV-1 transmission have yet to be fully understood. A research team led by Dr. Angela M. Amedee of Louisiana State University Health Sciences Center sought to investigate the early stages of HIV pathogenesis by studying the distribution of SIV RNA and DNA in infant macaques. SIV, or simian immunodeficiency virus, was thought to have mutated into HIV and crossed the species barrier to humans sometime in the last century.
The sample included two neonates and fifteen macaque infants (Macaca mulatta). Euthanizations were conducted at 24, 48, 72, and 96 hours and the spread of RNA and DNA was studied at multiple tissue sites, including the exposure site, lymph nodes (LNs), GI tract, lung, distal lymphoid tissues, systemic tissues, and the brain. Results from the neonates suggest that the virus spreads relatively quickly from the GI tract to the respiratory LNs. In just 48 hours for one neonate, retropharyngeal and mesenteric (GI) LNs had 7 and 9 SIV RNA copies/106 cells and 10 and 8 copies/106 cells in the lung and bronchial LNs respectively. The same neonate had 290, 100, and 80 copies/106 cells in the mesenteric LNs, lung, and bronchial LNs respectively. In the infant macaques, SIV RNA propagation was dependent mainly on time; tissue samples taken at 96 hours reveal significant replication. SIV RNA safely exceeded 1000 copies/106 cells in the LNs as well as the GI tract. Significant DNA propagation was found in oral cavity draining LNs (8 infants), the ileum (8 infants), as well as the lung (>8 infants). This distribution of DNA seems to suggest that the SIV makes it way by penetrating the LNs surrounding the oral mucosa, thus allowing it access to the GI tract and eventually the rest of the body.
Much work remains to be done on the spread of the SIV/HIV after exposure. Possible directions for future study may include uncovering the most common phenotypes among infected cells in a given tissue and studying alternative methods of viral entry. Perhaps the traditional anti-retroviral HIV therapy can be revamped given our new knowledge of the regions that SIV penetrates. Nevertheless, this research have the potential to facilitate improved treatment for HIV by enabling researchers to better understand its transmission.
- A. Amedee, et. al., Early sites of virus replication after oral siv infection of infant macaques: implications for pathogenesis. AIDS Research and Human Retroviruses (2018). doi: 10.1089/aid.2017.0169
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