Abstract
The development of an animal model of human immunodeficiency virus type 1 (HIV-1)/AIDS that is suitable for preclinical testing of antiretroviral therapy, vaccines, curative strategies, and studies of pathogenesis has been hampered by the human-specific tropism of HIV-1. Although simian immunodeficiency virus (SIV) or HIV-1/SIV chimeric viruses (SHIVs)-rhesus macaque models are excellent surrogates for AIDS research, the genetic differences between SIV or SHIV and HIV-1 limit their utility as model systems. The identification of innate retroviral restriction factors has increased our understanding about blockades to HIV-1 replication in macaques and provided a guide for the construction of macaque-tropic HIV-1 clones. However, while these viruses replicate in macaque cells in vitro, they are easily controlled and have not caused AIDS in host animals, indicating that we may not fully understand the restrictive barriers of innate immunity. In this review, we discuss recent findings regarding HIV-1 restriction factors, particularly as they apply to cross-species transmission of primate lentiviruses and the development of a macaque model of HIV-1/AIDS.
Highlights
A significant problem for testing novel antiretroviral drugs and vaccines against human immunodeficiency virus type 1 (HIV-1) has been the lack of an animal model due to the inability of the virus to replicate in species other than humans
A recent report suggests that simian immunodeficiency virus cpz (SIVcpz), the precursor of HIV-1, may cause AIDS
SIV chimeric viruses (SHIVs) chimeras revealed which HIV-1 genes are functional in macaque hosts, narrowing the determinants that may be critical for cross-species transmission of HIV-1 into macaques
Summary
A significant problem for testing novel antiretroviral drugs and vaccines against human immunodeficiency virus type 1 (HIV-1) has been the lack of an animal model due to the inability of the virus to replicate in species other than humans. A recent report suggests that simian immunodeficiency virus cpz (SIVcpz), the precursor of HIV-1, may cause AIDS in wild chimpanzees [1]. It is not clear how commonly this happens. Other nonhuman primate species, including Asian macaques that are used for the SIVmac AIDS model, have not proven to be susceptible to HIV-1. This narrow host range of HIV-1 has complicated the development of a nonhuman primate model of HIV-1 infection and disease. We review the literature about innate barriers to HIV-1 infection and application of this knowledge to developing a macaque model of HIV-1/AIDS
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