PMID- 19573243
OWN - NLM
STAT- MEDLINE
DCOM- 20090908
LR  - 20211020
IS  - 1742-4690 (Electronic)
IS  - 1742-4690 (Linking)
VI  - 6
IP  - Suppl 2
DP  - 2009 Jul 2
TI  - Evolution of SIV toward RANTES resistance in macaques rapidly progressing to AIDS 
      upon coinfection with HHV-6A.
PG  - 61
LID - 10.1186/1742-4690-6-61 [doi]
AB  - BACKGROUND: Progression to AIDS is often associated with the evolution of HIV-1 
      toward increased virulence and/or pathogenicity. Evidence suggests that a 
      virulence factor for HIV-1 is resistance to CCR5-binding chemokines, most notably 
      RANTES, which are believed to play a role in HIV-1 control in vivo. HIV-1 can 
      achieve RANTES resistance either by phenotypic switching from an exclusive CCR5 
      usage to an expanded coreceptor specificity, or by the acquisition of alternative 
      modalities of CCR5 usage. An infectious agent that might promote the evolution of 
      HIV-1 toward RANTES resistance is human herpesvirus 6A (HHV-6A), which is 
      frequently reactivated in HIV-1-infected patients and is a potent RANTES inducer 
      in lymphoid tissue. RESULTS: SIV isolates obtained from pig-tailed macaques (M. 
      nemestrina) after approximately one year of single infection with SIV(smE660) or 
      dual infection with SIV(smE660) and HHV-6A(GS) were characterized for their 
      growth capacity and sensitivity to HHV-6A- and RANTES-mediated inhibition in 
      human or macaque lymphoid tissues ex vivo. Four out of 4 HHV-6A-coinfected 
      macaques, all of which progressed to full-blown AIDS within 2 years of infection, 
      were found to harbor SIV variants with a reduced sensitivity to both HHV-6A and 
      RANTES, despite maintaining an exclusive CCR5 coreceptor specificity; viruses 
      derived from two of these animals replicated even more vigorously in the presence 
      of exogenous HHV-6A or RANTES. The SIV variants that emerged in HHV-6A-coinfected 
      macaques showed an overall reduced ex vivo replication capacity that was 
      partially reversed upon addition of exogenous RANTES, associated with suppressed 
      IL-2 and enhanced IFN-gamma production. In contrast, SIV isolates obtained from 
      two singly-infected macaques, none of which progressed to AIDS, maintained 
      HHV-6A/RANTES sensitivity, whereas the only AIDS progressor among singly-infected 
      macaques developed an SIV variant with partial HHV-6A/RANTES resistance and 
      increased replication capacity, associated with expanded coreceptor usage. 
      CONCLUSION: These results provide in vivo evidence of SIV evolution toward RANTES 
      resistance in macaques rapidly progressing to AIDS. RANTES resistance may 
      represent a common virulence factor allowing primate immunodeficiency 
      retroviruses to evade a critical mechanism of host antiviral defense.
FAU - Biancotto, Angelique
AU  - Biancotto A
AD  - Laboratory of Molecular and Cellular Biophysics, National Institute of Child 
      Health and Human Development, Bethesda, MD 20892, USA. biancoa@nhlbi.nih.gov
FAU - Grivel, Jean-Charles
AU  - Grivel JC
FAU - Lisco, Andrea
AU  - Lisco A
FAU - Vanpouille, Christophe
AU  - Vanpouille C
FAU - Markham, Phillip D
AU  - Markham PD
FAU - Gallo, Robert C
AU  - Gallo RC
FAU - Margolis, Leonid B
AU  - Margolis LB
FAU - Lusso, Paolo
AU  - Lusso P
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090702
PL  - England
TA  - Retrovirology
JT  - Retrovirology
JID - 101216893
RN  - 0 (Chemokine CCL5)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL5/*immunology
MH  - Herpesvirus 6, Human/*immunology
MH  - Humans
MH  - Leukocytes, Mononuclear/immunology/virology
MH  - Lymph Nodes/immunology/virology
MH  - Macaca
MH  - Organ Culture Techniques
MH  - Palatine Tonsil/immunology/virology
MH  - Roseolovirus Infections/*complications/immunology/virology
MH  - Simian Acquired Immunodeficiency Syndrome/*complications/immunology/*virology
MH  - Simian Immunodeficiency Virus/growth & development/*immunology/isolation & 
      purification
PMC - PMC2766956
EDAT- 2009/07/04 09:00
MHDA- 2009/09/09 06:00
PMCR- 2009/09/24
CRDT- 2009/07/04 09:00
PHST- 2009/03/19 00:00 [received]
PHST- 2009/07/02 00:00 [accepted]
PHST- 2009/07/04 09:00 [entrez]
PHST- 2009/07/04 09:00 [pubmed]
PHST- 2009/09/09 06:00 [medline]
PHST- 2009/09/24 00:00 [pmc-release]
AID - 1742-4690-6-61 [pii]
AID - 1742-4690-6-S2-I3 [pii]
AID - 10.1186/1742-4690-6-61 [doi]
PST - epublish
SO  - Retrovirology. 2009 Jul 2;6(Suppl 2):61. doi: 10.1186/1742-4690-6-61.