Neutralization-sensitive R5-tropic simian-human immunodeficiency virus SHIV-2873Nip, which carries env isolated from an infant with a recent HIV clade C infection.
Human immunodeficiency virus clade C (HIV-C) accounts for >56% of all HIV infections worldwide. To investigate vaccine safety and efficacy in nonhuman primates, a pathogenic, R5-tropic, neutralization-sensitive simian-human immunodeficiency virus (SHIV) carrying HIV-C env would be desirable. We have constructed SHIV-2873Ni, an R5-tropic SHIV carrying a primary pediatric HIV-C env gene isolated from a 2-month-old Zambian infant, who died within 1 year of birth. SHIV-2873Ni was constructed using SHIV-1157ipd3N4 (R. J. Song, A. L. Chenine, R. A. Rasmussen, C. R. Ruprecht, S. Mirshahidi, R. D. Grisson, W. Xu, J. B. Whitney, L. M. Goins, H. Ong, P. L. Li, E. Shai-Kobiler, T. Wang, C. M. McCann, H. Zhang, C. Wood, C. Kankasa, W. E. Secor, H. M. McClure, E. Strobert, J. G. Else, and R. M. Ruprecht. J. Virol. 80:8729-8738, 2006) as the backbone, since the latter contains additional NF-kappaB sites in the long terminal repeats to enhance viral replicative capacity. The parental virus, SHIV-2873Ni, was serially passaged through five rhesus monkeys (RMs); SHIV-2873Nip, the resulting passaged virus, was reisolated from the fourth recipient about 1 year postinoculation. SHIV-2873Nip was replication competent in RM peripheral blood mononuclear cells of all random donors tested and was exclusively R5 tropic, and its env gene clustered with HIV-C by phylogenetic analysis; its moderate [corrected] sensitivity to neutralization led to classification as a tier 2 [corrected] virus. Indian-origin RMs were inoculated by different mucosal routes, resulting in high peak viral RNA loads. Signs of virus-induced disease include depletion of gut CD4(+) T lymphocytes, loss of memory T cells in blood, and thrombocytopenia that resulted in fatal cerebral hemorrhage. SHIV-2873Nip is a highly replication-competent, mucosally transmissible, pathogenic R5-tropic virus that will be useful to study viral pathogenesis and to assess the efficacy of immunogens targeting HIV-C Env.
Siddappa
Nagadenahalli B
NB
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Song
Ruijiang
R
Kramer
Victor G
VG
Chenine
Agnès-Laurence
AL
Velu
Vijayakumar
V
Ong
Helena
H
Rasmussen
Robert A
RA
Grisson
Ricky D
RD
Wood
Charles
C
Zhang
Hong
H
Kankasa
Chipeppo
C
Amara
Rama Rao
RR
Else
James G
JG
Novembre
Francis J
FJ
Montefiori
David C
DC
Ruprecht
Ruth M
RM
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D018450:Disease Progression; D015752:Genes, env; D006678:HIV / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D015658:HIV Infections / Q000821:virology*; D006801:Humans; D007223:Infant; D008253:Macaca mulatta; D009500:Neutralization Tests; D010802:Phylogeny; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014779:Virus Replication
D017931:DNA Primers