Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6

Jean-Charles B. Grivel, Yoshinori Ito, Giovanni Fagà, Fabio Santoro, Farida Shaheen, Mauro S. Malnati, Wendy Fitzgerald, Paolo Lusso, Leonid Margolis

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

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 disease2-9. 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 progression12. Here we show that in human lymphoid tissue ex vivo13-15, 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 chemokine16, 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.

Original languageEnglish
Pages (from-to)1232-1235
Number of pages4
JournalNature Medicine
Volume7
Issue number11
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Human Herpesvirus 6
Tropics
Lymphoid Tissue
HIV-1
T-cells
Tissue
Chemical activation
HIV Infections
HIV
Macrophages
Chemokine Receptors
T-Lymphocytes
Acquired Immunodeficiency Syndrome
Ligands
Disease Progression

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Grivel, J-C. B., Ito, Y., Fagà, G., Santoro, F., Shaheen, F., Malnati, M. S., ... Margolis, L. (2001). Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6. Nature Medicine, 7(11), 1232-1235. https://doi.org/10.1038/nm1101-1232

Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6. / Grivel, Jean-Charles B.; Ito, Yoshinori; Fagà, Giovanni; Santoro, Fabio; Shaheen, Farida; Malnati, Mauro S.; Fitzgerald, Wendy; Lusso, Paolo; Margolis, Leonid.

In: Nature Medicine, Vol. 7, No. 11, 2001, p. 1232-1235.

Research output: Contribution to journalArticle

Grivel, J-CB, Ito, Y, Fagà, G, Santoro, F, Shaheen, F, Malnati, MS, Fitzgerald, W, Lusso, P & Margolis, L 2001, 'Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6', Nature Medicine, vol. 7, no. 11, pp. 1232-1235. https://doi.org/10.1038/nm1101-1232
Grivel, Jean-Charles B. ; Ito, Yoshinori ; Fagà, Giovanni ; Santoro, Fabio ; Shaheen, Farida ; Malnati, Mauro S. ; Fitzgerald, Wendy ; Lusso, Paolo ; Margolis, Leonid. / Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6. In: Nature Medicine. 2001 ; Vol. 7, No. 11. pp. 1232-1235.
@article{b2ebef2d46d4409fafa13c99499b411e,
title = "Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6",
abstract = "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 disease2-9. 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 progression12. Here we show that in human lymphoid tissue ex vivo13-15, 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 chemokine16, 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.",
author = "Grivel, {Jean-Charles B.} and Yoshinori Ito and Giovanni Fag{\`a} and Fabio Santoro and Farida Shaheen and Malnati, {Mauro S.} and Wendy Fitzgerald and Paolo Lusso and Leonid Margolis",
year = "2001",
doi = "10.1038/nm1101-1232",
language = "English",
volume = "7",
pages = "1232--1235",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6

AU - Grivel, Jean-Charles B.

AU - Ito, Yoshinori

AU - Fagà, Giovanni

AU - Santoro, Fabio

AU - Shaheen, Farida

AU - Malnati, Mauro S.

AU - Fitzgerald, Wendy

AU - Lusso, Paolo

AU - Margolis, Leonid

PY - 2001

Y1 - 2001

N2 - 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 disease2-9. 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 progression12. Here we show that in human lymphoid tissue ex vivo13-15, 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 chemokine16, 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.

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 disease2-9. 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 progression12. Here we show that in human lymphoid tissue ex vivo13-15, 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 chemokine16, 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.

UR - http://www.scopus.com/inward/record.url?scp=0035168719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035168719&partnerID=8YFLogxK

U2 - 10.1038/nm1101-1232

DO - 10.1038/nm1101-1232

M3 - Article

C2 - 11689888

AN - SCOPUS:0035168719

VL - 7

SP - 1232

EP - 1235

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 11

ER -