Arch Virol (2003) 148: 973–988
DOI 10.1007/s00705-002-0955-7
Infection of macaques with an R5-tropic SHIV
bearing a chimeric envelope carrying subtype E V3 loop
among subtype B framework
M. Kaizu
1,5,6
, H. Sato
2,3
,Y.Ami
4
, Y. Izumi
1,5
, T. Nakasone
1,5
, Y. Tomita
2
,
K. Someya
1
, Y. Takebe
3
, K. Kitamura
6
, O. Tochikubo
6
, and M. Honda
1,5
1
Vaccine Research and Development Group, AIDS Research Center, NIID, Tokyo, Japan
2
Division of Molecular Genetics, Tokyo, Japan
3
Laboratory of Molecular Virology and Epidemiology, AIDS Research Center,
NIID, Tokyo, Japan
4
Division of Experimental Animal Research, NIID, Tokyo, Japan
5
Development of HIV/AIDS Vaccine for HIV-1 Subtype E Project,
Japan Science and Technology Corporation (JST), Kawaguchi, Japan
6
Department of Public Health,Yokohama City University School of Medicine,
Yokohama, Japan
Received July 30, 2002; accepted November 13, 2002
Published online March 21, 2003
c
Springer-Verlag 2003
Summary. To establish simian/human immunodeficiency virus (SHIV) clones
bearing a chimeric envelope carrying subtype E V3 loop among subtype B enve-
lope, four subtype EV3 sequences were substituted into SHIV
MD14
, a SHIV clone
bearing an envelope derived from a CXCR4 (X4)/CCR5 (R5)-dual tropic subtype
B HIV-1 strain. SHIV-TH09V3, an only V3-chimera clone capable of replicat-
ing in human and macaque peripheral blood mononuclear cells (PBMCs), was
propagated in pig-tailed macaque PBMCs and in cynomolgus macaque splenic
mononuclear cells. The propagated virus stocks were intravenously inoculated
into respective macaque species. SHIV-TH09V3 infected both macaque species
as shown by plasma RNA viremia, isolated viruses from PBMCs and plasma,
and antibody production against viral proteins. To assess how the substituted V3
sequenceaffectedcoreceptorusage,SHIV-TH09V3stockspropagatedinvitroand
after isolation from macaques were verified for their corecepor usage by GHOST
cellsassay. SHIV-TH09V3maintainedR5-tropicphenotypebothinvitroandafter
isolation from macaques, in contrast to the X4/R5-dual tropic SHIV
MD14
. This
indicates the substitutedV3 sequence among the backbone of SHIV
MD14
governs
coreceptor usage. Future study of infecting macaques with SHIV-TH09V3 and
SHIV
MD14
will focus on differences of the outcome caused by the different V3
sequences in connection with coreceptor usage.