Human Immunodeficiency Virus Type 1 Derivative with 7% Simian Immunodeficiency Virus Genetic Content Is Able To Establish Infections in Pig-Tailed Macaques

Abstract

A human immunodeficiency virus type 1 (HIV-1) derivative (HIVNL-DT5R) containing sequences encoding a 7-amino-acid segment of CA and the entire vif gene from simian immunodeficiency virus (SIV) was previously shown to establish spreading infections in cultured macaque peripheral blood mononuclear cells. To assess its replicative and disease-inducing properties in vivo, HIVNL-DT5R was inoculated into pig-tailed macaques. HIVNL-DT5R generated plasma viremia in all five of the monkeys and elicited humoral responses against all of the HIV-1 structural proteins but did not cause CD4+ T-lymphocyte depletion or clinical disease. Additional adaptation will be required to optimize infectivity in vivo.

Generation of Rhesus Macaque-Tropic HIV-1 Clones That Are Resistant to Major Anti-HIV-1 Restriction Factors

“…It was shown previously that the in vivo replication of SIV is predictable from the virus susceptibility of PBMCs (62,63). Also, in a series of our studies, the better our HIV-1mt clones grew in PBMCs, the better they grew in the monkeys (20,24,64). Thus, it is expected that MN4/LSDQgtu will grow much better in RhM individuals, at least in the early infection phase, than the other HIV-1mt clones constructed.…”

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

“…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).…”

Productive Replication of vif -Chimeric HIV-1 in Feline Cells

“…More recently, HIV-1 clones in which only the vif gene or vif and capsid sequences from the SIVmac/SIVsm/HIV-2 lineage were introduced, which allowed the viruses to evade macaque intrinsic immunity defenses, were developed (23,24,30,33). In a promising recent iteration, peak HIV-1 viremia in the range of 10 5 to 10 6 RNA copies/ml followed by gradually declining replication for approximately 6 months was achieved in pig-tailed macaques with a vif-only chimera (23).…”