PMID- 19493994
OWN - NLM
STAT- MEDLINE
DCOM- 20090908
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 83
IP  - 16
DP  - 2009 Aug
TI  - Simian immunodeficiency virus SIVrcm, a unique CCR2-tropic virus, selectively 
      depletes memory CD4+ T cells in pigtailed macaques through expanded coreceptor 
      usage in vivo.
PG  - 7894-908
LID - 10.1128/JVI.00444-09 [doi]
AB  - Simian immunodeficiency virus SIVrcm, which naturally infects red-capped 
      mangabeys (RCMs), is the only SIV that uses CCR2 as its main coreceptor due to 
      the high frequency of a CCR5 deletion in RCMs. We investigated the dynamics of 
      SIVrcm infection to identify specific pathogenic mechanisms associated with this 
      major difference in SIV biology. Four pigtailed macaques (PTMs) were infected 
      with SIVrcm, and infection was monitored for over 2 years. The dynamics of in 
      vivo SIVrcm replication in PTMs was similar to that of other pathogenic and 
      nonpathogenic lymphotropic SIVs. Plasma viral loads (VLs) peaked at 10(7) to 
      10(9) SIVrcm RNA copies/ml by day 10 postinoculation (p.i.). A viral set point 
      was established by day 42 p.i. at 10(3) to 10(5) SIVrcm RNA copies/ml and lasted 
      up to day 180 p.i., when plasma VLs decreased below the threshold of detection, 
      with blips of viral replication during the follow-up. Intestinal SIVrcm 
      replication paralleled that of plasma VLs. Up to 80% of the CD4(+) T cells were 
      depleted by day 28 p.i. in the gut. The most significant depletion (>90%) 
      involved memory CD4(+) T cells. Partial CD4(+) T-cell restoration was observed in 
      the intestine at later time points. Effector memory CD4(+) T cells were the least 
      restored. SIVrcm strains isolated from acutely infected PTMs used CCR2 
      coreceptor, as reported, but expansion of coreceptor usage to CCR4 was also 
      observed. Selective depletion of effector memory CD4(+) T cells is in contrast 
      with predicted in vitro tropism of SIVrcm for macrophages and is probably due to 
      expansion of coreceptor usage. Taken together, these findings emphasize the 
      importance of understanding the selective forces driving viral adaptation to a 
      new host.
FAU - Gautam, Rajeev
AU  - Gautam R
AD  - Tulane National Primate Research Center, Covington, LA 70433, USA.
FAU - Gaufin, Thaidra
AU  - Gaufin T
FAU - Butler, Isolde
AU  - Butler I
FAU - Gautam, Aarti
AU  - Gautam A
FAU - Barnes, Mary
AU  - Barnes M
FAU - Mandell, Daniel
AU  - Mandell D
FAU - Pattison, Melissa
AU  - Pattison M
FAU - Tatum, Coty
AU  - Tatum C
FAU - Macfarland, Jeanne
AU  - Macfarland J
FAU - Monjure, Christopher
AU  - Monjure C
FAU - Marx, Preston A
AU  - Marx PA
FAU - Pandrea, Ivona
AU  - Pandrea I
FAU - Apetrei, Cristian
AU  - Apetrei C
LA  - eng
SI  - GDB/GQ267527
SI  - GENBANK/GQ267521
SI  - GENBANK/GQ267522
SI  - GENBANK/GQ267523
SI  - GENBANK/GQ267524
SI  - GENBANK/GQ267525
SI  - GENBANK/GQ267526
GR  - C06 RR12112/RR/NCRR NIH HHS/United States
GR  - G20 RR019628/RR/NCRR NIH HHS/United States
GR  - R01 AI064066/AI/NIAID NIH HHS/United States
GR  - G20 RR016930/RR/NCRR NIH HHS/United States
GR  - P51 RR000164/RR/NCRR NIH HHS/United States
GR  - RR013466/RR/NCRR NIH HHS/United States
GR  - G20 RR018397/RR/NCRR NIH HHS/United States
GR  - RR018397/RR/NCRR NIH HHS/United States
GR  - R01 AI065325/AI/NIAID NIH HHS/United States
GR  - P20 RR020159/RR/NCRR NIH HHS/United States
GR  - RR05169/RR/NCRR NIH HHS/United States
GR  - G20 RR013466/RR/NCRR NIH HHS/United States
GR  - RR019628/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090603
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CCR4 protein, human)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, CCR4)
RN  - 0 (Receptors, HIV)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*immunology/virology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - HIV/physiology
MH  - HIV Infections/*immunology/virology
MH  - Humans
MH  - Leukocytes, Mononuclear/metabolism/virology
MH  - Macaca nemestrina
MH  - Molecular Sequence Data
MH  - Receptors, CCR2/genetics/*immunology
MH  - Receptors, CCR4/genetics/immunology
MH  - Receptors, HIV/genetics/*immunology
MH  - Simian Acquired Immunodeficiency Syndrome/genetics/*immunology/virology
MH  - Simian Immunodeficiency Virus/genetics/immunology/*physiology
MH  - Viral Load
MH  - Virus Internalization
MH  - Virus Replication
PMC - PMC2715763
EDAT- 2009/06/06 09:00
MHDA- 2009/09/09 06:00
PMCR- 2010/02/01
CRDT- 2009/06/05 09:00
PHST- 2009/06/05 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/09/09 06:00 [medline]
PHST- 2010/02/01 00:00 [pmc-release]
AID - JVI.00444-09 [pii]
AID - 0444-09 [pii]
AID - 10.1128/JVI.00444-09 [doi]
PST - ppublish
SO  - J Virol. 2009 Aug;83(16):7894-908. doi: 10.1128/JVI.00444-09. Epub 2009 Jun 3.