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Titolo:
Derivation and biological characterization of a molecular clone of SHIVKU-2 that causes AIDS, neurological disease, and renal disease in rhesus macaques
Autore:
Liu, ZQ; Muhkerjee, S; Sahni, M; McCormick-Davis, C; Leung, K; Li, Z; Gattone, VH; Tian, CQ; Doms, RW; Hoffman, TL; Raghavan, R; Narayan, O; Stephens, EB;
Indirizzi:
Univ Kansas, Med Ctr, Marion Merrell Dow Lab Viral Pathogenesis, Kansas City, KS 66160 USA Univ Kansas Kansas City KS USA 66160 hogenesis, Kansas City, KS 66160 USA Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA Univ Kansas Kansas City KS USA 66160 & Immunol, Kansas City, KS 66160 USA Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66160 USA Univ Kansas Kansas City KS USA 66160 Cell Biol, Kansas City, KS 66160 USA Univ Penn, Dept Lab Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 t Lab Med, Philadelphia, PA 19104 USA
Titolo Testata:
VIROLOGY
fascicolo: 2, volume: 260, anno: 1999,
pagine: 295 - 307
SICI:
0042-6822(19990801)260:2<295:DABCOA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; PIG-TAILED MACAQUES; COMPLETE NUCLEOTIDE-SEQUENCE; ENZYMATIC AMPLIFICATION; DIVERSE HUMAN; HIV-1; INFECTION; TYPE-1; RECEPTORS; MONKEYS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Stephens, EB Univ Kansas, Med Ctr, Marion Merrell Dow Lab Viral Pathogenesis, Kansas City, KS 66160 USA Univ Kansas Kansas City KS USA 66160 nsas City, KS 66160 USA
Citazione:
Z.Q. Liu et al., "Derivation and biological characterization of a molecular clone of SHIVKU-2 that causes AIDS, neurological disease, and renal disease in rhesus macaques", VIROLOGY, 260(2), 1999, pp. 295-307

Abstract

Previously, we described the derivation of a pathogenic strain of simian-human immunodeficiency virus (SHIVKU-2) consisting of the tat, rev, vpu, andenv genes of HIV-1 (strain HXB2) in a genetic background of SIV(mac)239 that causes AIDS and productive infection of the CNS in rhesus macaques (Macca mulatta) (Raghavan et al., 1997 Brain Pathol. 7, 851-861). We report hereon the characterization of a molecular clone of SHIVKU-2, designated SHIVKU-2MC4, that caused CD4(+) T cell loss as well as neurological and renal disease in macaques. DNA sequence analysis of selected SIV regions of SHIVKU-2MC4 revealed 10 nucleotide changes in the LTR, whereas Gag, Vif, Vpr, Vpx,and Nef had 1, 1, 1, 2, and 13 predicted amino acid substitutions, respectively, compared to SIV(mac)239. DNA sequence analysis of HIV-1 derived regions of SHIVKU-2MC4 revealed 2, 1, 2, and 18 predicted amino acid substitutions in the Tat, Rev, Vpu, and Env proteins, respectively, when compared to SHIV-4. Unlike the parental SHIV-4, which is not tropic for macrophages, SHIVKU-2MC4 replicated efficiently in macrophage cultures as determined by p27 assays. However, despite the numerous changes in the Env protein and newly acquired tropism for macrophages, SHIVKU-2MC4, like the parental SHIV-4, used CXCR4 exclusively as its coreceptor for entry into susceptible cells. Inoculation of SHIVKU-2MC4 into two rhesus macaques resulted in severe infection in which the numbers of circulating CD4(+) T cells in the blood declined rapidly by 2 weeks postinoculation and virus producing cells in the peripheral blood mononuclear cells were identified throughout the course of infection. At the lime of euthanasia (20 and 22 weeks), both macaques had lost a significant amount of weight and had no circulating CD4(+) T cells. In addition, one macaque developed intension tremors and uncoordinated movements. Virological examination of tissues at necropsy revealed active virus replication in both lymphoid and nonlymphoid tissues such as the lung and brain. Histological examination revealed that the induced immunodeficiency wasassociated with lymphoid depletion of the lymph nodes and spleen, opportunistic infections, lentiviral encephalitis, and severe glomerulosclerosis ofthe kidney. This molecular clone will serve as the basis for analyzing themolecular determinants through which SHIVKU-2 causes severe CD4(+) T cell loss, neurological disease, and SHIV nephropathy in rhesus macaques. (C) 1999 Academic Press.

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Documento generato il 30/11/20 alle ore 03:02:16