PMID- 11689888
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20071115
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 7
IP  - 11
DP  - 2001 Nov
TI  - Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human 
      herpesvirus 6.
PG  - 1232-5
AB  - HIV-1 infects target cells via a receptor complex formed by CD4 and a chemokine 
      receptor, primarily CCR5 or CXCR4 (ref. 1). Commonly, HIV-1 transmission is 
      mediated by CCR5-tropic variants, also designated slow/low, non-syncytia-inducer 
      or macrophage-tropic, which dominate the early stages of HIV-1 infection and 
      frequently persist during the entire course of the disease. In contrast, HIV-1 
      variants that use CXCR4 are typically detected at the later stages, and are 
      associated with a rapid decline in CD4+ T cells and progression to AIDS (refs. 
      2,7-11). Disease progression is also associated with the emergence of concurrent 
      infections that may affect the course of HIV disease by unknown mechanisms. A 
      lymphotropic agent frequently reactivated in HIV-infected patients is human 
      herpesvirus 6 (HHV-6), which has been proposed as a cofactor in AIDS progression. 
      Here we show that in human lymphoid tissue ex vivo, HHV-6 affects HIV-1 infection 
      in a coreceptor-dependent manner, suppressing CCR5-tropic but not CXCR4-tropic 
      HIV-1 replication, as shown with both uncloned viral isolates and isogenic 
      molecular chimeras. Furthermore, we demonstrate that HHV-6 increases the 
      production of the CCR5 ligand RANTES ('regulated upon activation, normal T-cell 
      expressed and secreted'), the most potent HIV-inhibitory CC chemokine, and that 
      exogenous RANTES mimics the effects of HHV-6 on HIV-1, providing a mechanism for 
      the selective blockade of CCR5-tropic HIV-1. Our data suggest that HHV-6 may 
      profoundly influence the course of HIV-1 infection.
FAU - Grivel, J C
AU  - Grivel JC
AD  - Laboratory of Cellular and Molecular Biophysics, National Institute of Child 
      Health and Human Development, Bethesda, Maryland, USA.
FAU - Ito, Y
AU  - Ito Y
FAU - Faga, G
AU  - Faga G
FAU - Santoro, F
AU  - Santoro F
FAU - Shaheen, F
AU  - Shaheen F
FAU - Malnati, M S
AU  - Malnati MS
FAU - Fitzgerald, W
AU  - Fitzgerald W
FAU - Lusso, P
AU  - Lusso P
FAU - Margolis, L
AU  - Margolis L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Chemokine CCL5)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Chemokine CCL5/biosynthesis/pharmacology
MH  - Culture Techniques
MH  - HIV Infections/complications/etiology/virology
MH  - HIV-1/drug effects/genetics/*pathogenicity/*physiology
MH  - Herpesvirus 6, Human/*physiology
MH  - Humans
MH  - Lymphoid Tissue/immunology/virology
MH  - Receptors, CCR5/physiology
MH  - Receptors, CXCR4/physiology
MH  - Roseolovirus Infections/complications/etiology/virology
MH  - Virus Replication/drug effects
EDAT- 2001/11/02 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/02 10:00
PHST- 2001/11/02 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/02 10:00 [entrez]
AID - nm1101-1232 [pii]
AID - 10.1038/nm1101-1232 [doi]
PST - ppublish
SO  - Nat Med. 2001 Nov;7(11):1232-5. doi: 10.1038/nm1101-1232.