Animal models for HIV/AIDS research

Animal models are essential for testing antiretroviral drugs to treat HIV infection of humans and for acquiring the basic scientific knowledge that will ultimately be needed to develop a safe and effective vaccine against HIV-1.Owing to the narrow host range of HIV, HIV-1 infection of mice that have been reconstituted with a human immune system (humanized mice) and simian immunodeficiency virus (SIV) infection of macaques are used as surrogate models for studying HIV-1 infection of humans.There is no single animal model for AIDS, but rather a collection of host species and viruses that can be used depending on the question to be addressed.A number of humanized mouse models have been developed using different genetic backgrounds and engraftment with various human tissues. Whereas humanized mice make it possible to model HIV-1 infection of human cells in vivo and to design studies using genetically identical animals, these models are limited in their ability to replicate the effects of HIV-1 on non-haematopoietic tissues and to recreate basic features of HIV-1 disease in humans.Infection of Asian macaques with certain SIV or simian–human immunodeficiency virus (SHIV) recombinants results in gradual CD4+ T cell depletion and progression to AIDS, similar to HIV infection of humans. Thus, SIV and SHIV infection of macaques are currently the best, most widely accepted models for AIDS research.Genetic differences between macaque species, and in some cases between geographically distinct populations of the same species, can dramatically affect the outcome of SIV and SHIV infections and are important considerations in the use of these models.There is now considerable interest in engineering HIV-1 to overcome the barriers to HIV-1 replication in macaques. These barriers are imposed by the apolipoprotein B-editing catalytic subunit-like 3 (APOBEC3) proteins, by tripartite-motif-containing protein 5 (TRIM5) variants and by tetherin, all of which are HIV restriction factors. The development of minimally modified simian-tropic strains of HIV-1 that can reproducibly cause disease in macaques might eventually allow direct efficacy testing of antiretroviral drugs and vaccines in non-human primates.