Editorial [Hot Topic: Simian Immunodeficiency Virus Pathogenesis (Guest Editor: Donald Sodora)]

The etiologic agent that causes human AIDS was identified in 1981. Only a few years later Rhesus macaques at the New England Primate Center were observed exhibiting clinical signs representative of AIDS, leading to the isolation and identification of the simian immunodeficiency virus (SIV). Since that time, numerous studies have been undertaken utilizing the SIV/monkey model and a range of pathogenic outcomes identified due to genetic, virologic and immunologic differences. The distinct disease outcomes are quite evident when assessing the SIV infection in different monkey species. The majority of monkey species in Africa harbor SIV infections in the wild, and have been termed SIV natural host species. Sooty mangabeys (West Africa) and African green monkeys (found throughout Africa) are two of the more commonly studied SIV natural hosts. SIV is able to replicate to high levels in the natural host species yet the virus and host generally coexist, without exhibiting any clinical signs of simian AIDS. In contrast, macaques are from Asia and are not naturally infected with SIV in the wild. Therefore, SIV infection of macaques represent a cross-species transmission of the virus and in this regard is similar to HIV in humans. The SIV infection of macaques is similar to infectio of natural hosts as it also results in high levels of viral replication, however there are also clear indications of immune dysfunction commonly seen in AIDS patients (CD4 T cell decline, wasting, opportunistic infections). Although a small number of macaques are able to resist progression to AIDS, the vast majority of SIV infected macaques develop AIDS clinical signs and die by 6 months to 2 years post-infection. In this issue of Current HIV Research, three reviews assess various aspects of the infection of natural host species. Liovat et al. provide a clear assessment of the similarities and differences between the SIV infection in pathogenic and nonpathogenic primate hosts. One of the key findings is that during the earliest times post-infection SIV infections are similar in all species, however nonpathogenic infections distinguish themselves during the chronic phase of the infection when elements of immune activation and subsequent immune dysfunction are suppressed. Pereira and Ansari expanded upon the natural host analysis by assessing the role of innate cell subsets, NK cells and DCs, in keeping natural host species from progressing to AIDS. Pandrea et al. provide a more complete understanding of the nonpathogenic infection models by providing evidence that these host species can, under some circumstances develop clinical signs of simian AIDS. Based on these rare cases in more aged nonpathogenic species the authors of this review suggest that we should more accurately refer to natural hosts of SIV as being ‘persistently nonprogressive’. Six of the reviews assess and provide key insights into the pathogenic SIV infection of macaques. While the reviews have an overall focus that is immunologic in nature, they also provide information with regard to how the SIV infection itself is the trigger and underlying force that propels SIV-positive macaques toward simian AIDS. Cheng-Mayer et al. describe how coreceptor utilization impacts disease progression in the SIV/SHIV model, with a focus on the impact of coreceptor switching. Abel assesses the SIV macaque model for its use for studying pediatric SIV infections addressing aspects of transmission and immunologic implications of SIV/HIV infection of newborns. The ability of SIV/HIV infections to impact the functionality of plasmacytoid DCs is investigated by Wijewardana et al. Whereas Reinhart et al. focus on how dysregulation of chemokines impacts disease progression in SIV infected macaques. Burwitz et al. describe how studying Mauritian Cynomolgus macques, which have simple MHC genetics, might provide a model for utilizing lymphocyte adoptive transfer studies to better understand how to improve vaccine design. And finally, Leone et al. describes how cytokines that can impact T cell homeostasis are being utilized as both immune therapeutics and vaccine immune modulators in the SIV macaque model.