Derivation and Biological Characterization of a Molecular Clone of SHIVKU-2 That Causes AIDS, Neurological Disease, and Renal Disease in Rhesus Macaques

摘要: Abstract Previously, we described the derivation of a pathogenic strain simian–human immunodeficiency virus (SHIV KU-2 ) consisting tat, rev, vpu, and env genes HIV-1 (strain HXB2) in genetic background SIV mac 239 that causes AIDS productive infection CNS rhesus macaques ( Macca mulatta (Raghavan et al., 1997, Brain Pathol. 7, 851–861). We report here on characterization molecular clone SHIV , designated KU-2MC4 caused CD4 + T cell loss as well neurological renal disease macaques. DNA sequence analysis selected regions revealed 10 nucleotide changes LTR, whereas Gag, Vif, Vpr, Vpx, Nef had 1, 2, 13 predicted amino acid substitutions, respectively, compared to 239. derived 18 substitutions Tat, Rev, Vpu, Env proteins, when SHIV-4. Unlike parental SHIV-4, which is not tropic for macrophages, replicated efficiently macrophage cultures determined by p27 assays. However, despite numerous protein newly acquired tropism like used CXCR4 exclusively its coreceptor entry into susceptible cells. Inoculation two resulted severe numbers circulating cells blood declined rapidly 2 weeks postinoculation producing peripheral mononuclear were identified throughout course infection. At time euthanasia (20 22 weeks), both lost significant amount weight no In addition, one macaque developed intension tremors uncoordinated movements. Virological examination tissues at necropsy active replication lymphoid nonlymphoid such lung brain. Histological induced was associated with depletion lymph nodes spleen, opportunistic infections, lentiviral encephalitis, glomerulosclerosis kidney. This will serve basis analyzing determinants through loss, disease, nephropathy