Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells

Amino acid alterations in Gag that confer the ability to grow in simian cells on HIV-1 are located at a narrow CA region

“…A monkey-tropic infectious DNA clone of HIV -1 designated NL-DT5R has been previously described (2). An infectious clone designated NL-DT5R/4-3 is a derivative of NL-DT5R carrying CA of NL4-3, and grows more poorly than NL-DT5R in simian HSC-F cells (4).…”

“…To conquer this difficulty, we have recently generated a monkey-tropic HIV-1 designated NL-DT5R (1)(2)(3). Its genome contains a gag sequence encoding simian immunodeficiency virus from rhesus monkeys (SIVmac) capsid (CA) element, corresponding to the HIV-1 cyclophilin A (CypA) -binding loop, and the entire SIVmac vif gene (2). However, by subsequent studies, NL -DT5R was found to grow in simian cells more poorly both in vitro and in vivo than a standard SIVmac designated SIVmac 239, which induces the AIDS in monkeys and is widely used for model studies of HIV-1/AIDS.…”

“…HIV-1 infects and causes disease only in humans. To conquer this difficulty, we have recently generated a monkey-tropic HIV-1 designated NL-DT5R (1)(2)(3). Its genome contains a gag sequence encoding simian immunodeficiency virus from rhesus monkeys (SIVmac) capsid (CA) element, corresponding to the HIV-1 cyclophilin A (CypA) -binding loop, and the entire SIVmac vif gene (2).…”

Retroviral Host Cell Factors: TRIM5, APOBEC3G and Cyclophilins

“…This restriction is thought to be the same step in the retrovirus life cycle where CypA works (Braaten et al, 1996b). Indeed, Analysis of CypAbinding region of CA with chimeric viruses of HIV-1 and SIV showed the viral determinant for species-specificity (Berthoux et al, 2004;Bukovsky et al, 1997;Cowan et al, 2002; www.intechopen.com Dorfman and Gottlinger, 1996;Hatziioannou et al, 2004a;Hatziioannou et al, 2006;Ikeda et al, 2004;Kamada et al, 2006;Kootstra et al, 2003;Owens et al, 2004;Owens et al, 2003;Sayah et al, 2004;Shibata et al, 1991;Shibata et al, 1995;Stremlau et al, 2004;Towers et al, 2003). Human CypA is required for efficient HIV-1 infection but not SIV.…”

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

“…We must go behind the outward form to grasp the inner meaning of the phenomenon, i.e., the species-specificity. On the collective basis of molecular and biochemical studies performed by us and others so far, we recently have constructed a series of HIV-1 derivative clones tropic for macaque cells and/or macaques (Hatcho et al, 2008;Igarashi et al, 2007;Kamada et al, 2006Kamada et al, , 2009Kuroishi et al, 2009;Nomaguchi et al, 2008a;Saito et al, 2011;Yamashita et al, 2008), and are currently further modifying them for in vivo studies (our unpublished results). The viruses we have generated carry a minimal sequence of SIVmac, and overcome at least some species barriers.…”