Macaque-Tropic HIV-1 Derivatives: A Novel Experimental Approach to Understand Viral Replication and Evolution in Vivo

Abstract

The use of animal models in the study of human diseases is obviously important. Fundamental properties of the disease can be investigated analytically and thoroughly by this approach, contributing much to the progress of basic science as well as clinical medicine (Nomaguchi & Adachi, 2010). Researchers in various specialties, therefore, have made every effort to establish animal models for human diseases including those caused by infectious agents. Acquired immunodeficiency syndrome (AIDS) of humans has long been one of the major targets for the model study in appropriate animals. However, human immunodeficiency virus type 1 (HIV-1) itself, the predominant causative virus of human AIDS, can not be used due to its very narrow host range. Because HIV-1 has adapted itself dexterously from the ancestral virus to replicate, persist and spread strictly in humans, it is very unique among various primate immunodeficiency viruses and no good counterparts are available in nature (Desrosiers, 2007; Kirchhoff, 2009; Sauter et al., 2009). Therefore, it can be concluded that practical and meaningful animal systems of non-alternative nature for HIV-1 study do not exist at all to date, although there are pre-existing animal models of some significance. HIV-1 does not replicate in animal species except for chimpanzees and humans (Nomaguchi et al., 2008a). Animals frequently used for our experiments on virology, such as rodents and nonhuman primates, are not exceptions to this barrier. However, if we are to search for, develop and establish a fruitful animal model system for HIV-1 research, nonhuman primates are considered to be most suited, for HIV-1 is best fitted with humans and some apes. Ever since the discovery of HIV-1 (Barre-Sinoussi et al., 1983), many prominent researchers keen on understanding its biology and molecular biology have done investigations extensively to elucidate the bases underlying the species-specificity unique to HIV-1. These studies have highlighted the presence of potent anti-HIV-1 factors in nonhuman cells that efficiently restrict or even abolish the replication of HIV-1 and successfully raised an epoch-making notion of the intrinsic immunity (Andrew & Strebel, 2010; Arhel & Kirchhoff, 2010; Ayinde et al., 2010; Bergamaschi & Pancino, 2010; Douglas et al., 2010; Fujita et al., 2010; Huthoff & Towers, 2008; Kirchhoff, 2010; Luban, 2007; Malim & Emerman, 2008; Nakayama & Shioda, 2010; Nomaguchi et al., 2008a, 2008b; Planelles & Barker, 2010; Sauter et al., 2010; Strebel et al., 2009; Towers, 2007). Cellular factors shoulder