Molecularly cloned SHIV-1157ipd3N4: a highly replication- competent, mucosally transmissible R5 simian-human immunodeficiency virus encoding HIV clade C Env.
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.
Song
R J
RJ
Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Chenine
A-L
AL
Rasmussen
R A
RA
Ruprecht
C R
CR
Mirshahidi
S
S
Grisson
R D
RD
Xu
W
W
Whitney
J B
JB
Goins
L M
LM
Ong
H
H
Li
P-L
PL
Shai-Kobiler
E
E
Wang
T
T
McCann
C M
CM
Zhang
H
H
Wood
C
C
Kankasa
C
C
Secor
W E
WE
McClure
H M
HM
Strobert
E
E
Else
J G
JG
Ruprecht
R M
RM
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
C095085:CXCR5 protein, human; D015686:Gene Products, env; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine