title: Molecularly cloned SHIV-1157ipd3N4: a highly replication- competent, mucosally transmissible R5 simian-human immunodeficiency virus encoding HIV clade C Env.
abstract: Human immunodeficiency virus type 1 (HIV-1) clade C causes >50% of all HIV infections worldwide, and an estimated 90% of all transmissions occur mucosally with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade C env is highly desirable to evaluate candidate AIDS vaccines in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD4(+) T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a naïve animal induced memory T-cell depletion and thrombocytopenia within 3 months in the recipient. In parallel, genomic DNA from the blood donor was amplified to generate the late proviral clone SHIV-1157ipd3. To increase the replicative capacity of SHIV-1157ipd3, an extra NF-kappaB binding site was engineered into its 3' long terminal repeat, giving rise to SHIV-1157ipd3N4. This virus was exclusively R5 tropic and replicated more potently in rhesus peripheral blood mononuclear cells than SHIV-1157ipd3 in the presence of tumor necrosis factor alpha. Rhesus macaques of Indian and Chinese origin were next inoculated intrarectally with SHIV-1157ipd3N4; this virus replicated vigorously in both sets of monkeys. We conclude that SHIV-1157ipd3N4 is a highly replication-competent, mucosally transmissible R5 SHIV that represents a valuable tool to test candidate AIDS vaccines targeting HIV-1 clade C Env.
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Song
authors.forename: A-L
authors.initials: AL
authors.lastname: Chenine
authors.forename: R A
authors.initials: RA
authors.lastname: Rasmussen
authors.forename: C R
authors.initials: CR
authors.lastname: Ruprecht
authors.forename: S
authors.initials: S
authors.lastname: Mirshahidi
authors.forename: R D
authors.initials: RD
authors.lastname: Grisson
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: J B
authors.initials: JB
authors.lastname: Whitney
authors.forename: L M
authors.initials: LM
authors.lastname: Goins
authors.forename: H
authors.initials: H
authors.lastname: Ong
authors.forename: P-L
authors.initials: PL
authors.lastname: Li
authors.forename: E
authors.initials: E
authors.lastname: Shai-Kobiler
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: C M
authors.initials: CM
authors.lastname: McCann
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Wood
authors.forename: C
authors.initials: C
authors.lastname: Kankasa
authors.forename: W E
authors.initials: WE
authors.lastname: Secor
authors.forename: H M
authors.initials: HM
authors.lastname: McClure
authors.forename: E
authors.initials: E
authors.lastname: Strobert
authors.forename: J G
authors.initials: JG
authors.lastname: Else
authors.forename: R M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000285:Administration, Rectal; D000595:Amino Acid Sequence; D000818:Animals; D002678:Chimera; D003001:Cloning, Molecular; D015686:Gene Products, env / Q000235:genetics; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007223:Infant; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*; D014779:Virus Replication
chemical_list: C095085:CXCR5 protein, human; D015686:Gene Products, env; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine