Non-human primates in HIV research: Achievements, limits and alternatives

Abstract

An ideal model for HIV-1 research is still unavailable. However, infection of non-human primates (NHP), such as macaques, with Simian Immunodeficiency Virus (SIV) recapitulates most virological, immunological and clinical hallmarks of HIV infection in humans. It has become the most suitable model to study the mechanisms of transmission and physiopathology of HIV/AIDS. On the other hand, natural hosts of SIV, such as African green monkeys and sooty mangabeys that when infected do not progress to AIDS, represent an excellent model to elucidate the mechanisms involved in the capacity of controlling inflammation and disease progression. The use of NHP-SIV models has indeed enriched our knowledge in the fields of: i) viral transmission and viral reservoirs, ii) early immune responses, iii) host cell-virus interactions in tissues, iv) AIDS pathogenesis, v) virulence factors, vi) prevention and vii) drug development. The possibility to control many variables during experimental SIV infection, together with the resemblance between SIV and HIV infections, make the NHP model the most appropriate, so far, for HIV/AIDS research. Nonetheless, some limitations in using these models have to be considered. Alternative models for HIV/AIDS research, such as humanized mice and recombinant forms of HIV-SIV viruses (SHIV) for NHP infection, have been developed. The improvement of SHIV viruses that mimic even better the natural history of HIV infection and of humanized mice that develop a greater variety of human immune cell lineages, is ongoing. None of these models is perfect, but they allow contributing to the progress in managing or preventing HIV infection.

CpG Frequency in the 5′ Third of the env Gene Determines Sensitivity of Primary HIV-1 Strains to the Zinc-Finger Antiviral Protein

“…2B) and may thus have evolved reduced ZAP sensitivity despite the acquisition of higher CpG frequencies. SIVsmm has also been transmitted to rhesus macaques, giving rise to SIVmac, which causes rapid AIDS-like disease in this nonnatural host (22,23). Three strains of SIVmac were relatively resistant to ZAP ( Fig.…”

Natural pathology of the captive chimpanzee (Pan troglodytes): A 35‐year review

“…Although several chimpanzees in this study group were chronically infected with HBV, HCV, and HIV, we did not find any statistical correlation between viral status and liver diseases. This is not an unexpected finding given that chimpanzees infected with these viruses rarely develop clinically significant disease . Despite extensive control measures, nematodiasis (pinworms; Enterobius spp .)…”

“…This is not an unexpected finding given that chimpanzees infected with these viruses rarely develop clinically significant disease. [99][100][101] Despite extensive control measures, nematodiasis (pinworms; Enterobius spp.) remains prevalent in our colony and other captive colonies.…”

Systemic DPP4 activity is reduced during primary HIV‐1 infection and is associated with intestinal RORC+CD4+ cell levels: a surrogate marker candidate of HIV‐induced intestinal damage

“…To do this, we took advantage of animal models to measure DPP4 expression in distinct compartments of the gut. We compared DPP4 mRNA expression in the pathogenic model of HIV, that is, rhesus macaques (MAC) infected by SIVmac, to the non‐pathogenic model, that is, AGM infected by SIVagm . AGM are known to preserve Th17 levels in the gut and to maintain an intact intestinal barrier despite high viraemia .…”