Infection of γ/δ T lymphocytes by human herpesvirus 6: Transcriptional induction of CD4 and susceptibility to HIV infection

Paolo Lusso, Alfredo Garzino-Demo, Richard W. Crowley, Mauro S. Malnati

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Human herpesvirus 6 (HHV-6), a T-lymphotropic human herpesvirus, is a potentially immunosuppressive agent that has been suggested to play a role as a cofactor in the natural history of human immunodeficiency virus (HIV) infection. We studied the interactions between HHV-6 and γ/δ T lymphocytes, a subset of T cells involved in the protective immune response against specific microorganisms. Polyclonal γ/δ T cell populations, purified from the peripheral blood of healthy adults and activated in vitro with phytohemagglutinin, were exposed to HHV-6, strain GS (subgroup A), at the approximate multiplicity of infection (MOI) of 1. Signs of virus replication were detected as early as 72 h after infection, as documented by immunofluorescence, electron microscopy, and transmission of extracellular virus. Progression of the infection was associated with the appearance of typical cytomorphological changes and, eventually, massive cell death. In contrast, no signs of infection or cytopathic effects were detected after exposure of γ/δ T lymphocytes to HHV-7, a CD4+ T-lymphotropic virus closely related to HHV-6. Polyclonal γ/δ T cells displayed cytolytic activity against both autologous and heterologous target cells infected with HHV-6 and maintained this activity for at least 72 h after infection with HHV-6, despite the high MOI used. As previously documented in mature CD8+ α/β T cells and natural killer cells, HHV-6 infection induced γ/δ T lymphocytes to express de novo CD4 messenger RNA and protein, as detected by reverse transcriptase-polymerase chain reaction and fluorocytometry, respectively. Whereas purified CD4- γ/δ T cell populations were per se refractory to HIV infection, they became susceptible to productive infection by HIV-1, strain IIIB, after induction of CD4 expression by HHV-6. These results demonstrate that γ/δ T cells can be directly targeted and killed by a herpesvirus and may have implications for the potential role of HHV-6 in AIDS.

Original languageEnglish
Pages (from-to)1303-1310
Number of pages8
JournalJournal of Experimental Medicine
Volume181
Issue number4
DOIs
Publication statusPublished - Apr 1 1995

Fingerprint

Human Herpesvirus 6
Virus Diseases
HIV
T-Lymphocytes
Infection
Herpesviridae
Human Herpesvirus 7
Viruses
Herpesviridae Infections
T-Lymphocyte Subsets
Phytohemagglutinins
Immunosuppressive Agents
Virus Replication
Natural History
Reverse Transcriptase Polymerase Chain Reaction
Fluorescence Microscopy
Natural Killer Cells
Population
HIV-1
Electron Microscopy

ASJC Scopus subject areas

  • Immunology

Cite this

Infection of γ/δ T lymphocytes by human herpesvirus 6 : Transcriptional induction of CD4 and susceptibility to HIV infection. / Lusso, Paolo; Garzino-Demo, Alfredo; Crowley, Richard W.; Malnati, Mauro S.

In: Journal of Experimental Medicine, Vol. 181, No. 4, 01.04.1995, p. 1303-1310.

Research output: Contribution to journalArticle

@article{a378ab04bb5540b8a497c40bd57c9ae9,
title = "Infection of γ/δ T lymphocytes by human herpesvirus 6: Transcriptional induction of CD4 and susceptibility to HIV infection",
abstract = "Human herpesvirus 6 (HHV-6), a T-lymphotropic human herpesvirus, is a potentially immunosuppressive agent that has been suggested to play a role as a cofactor in the natural history of human immunodeficiency virus (HIV) infection. We studied the interactions between HHV-6 and γ/δ T lymphocytes, a subset of T cells involved in the protective immune response against specific microorganisms. Polyclonal γ/δ T cell populations, purified from the peripheral blood of healthy adults and activated in vitro with phytohemagglutinin, were exposed to HHV-6, strain GS (subgroup A), at the approximate multiplicity of infection (MOI) of 1. Signs of virus replication were detected as early as 72 h after infection, as documented by immunofluorescence, electron microscopy, and transmission of extracellular virus. Progression of the infection was associated with the appearance of typical cytomorphological changes and, eventually, massive cell death. In contrast, no signs of infection or cytopathic effects were detected after exposure of γ/δ T lymphocytes to HHV-7, a CD4+ T-lymphotropic virus closely related to HHV-6. Polyclonal γ/δ T cells displayed cytolytic activity against both autologous and heterologous target cells infected with HHV-6 and maintained this activity for at least 72 h after infection with HHV-6, despite the high MOI used. As previously documented in mature CD8+ α/β T cells and natural killer cells, HHV-6 infection induced γ/δ T lymphocytes to express de novo CD4 messenger RNA and protein, as detected by reverse transcriptase-polymerase chain reaction and fluorocytometry, respectively. Whereas purified CD4- γ/δ T cell populations were per se refractory to HIV infection, they became susceptible to productive infection by HIV-1, strain IIIB, after induction of CD4 expression by HHV-6. These results demonstrate that γ/δ T cells can be directly targeted and killed by a herpesvirus and may have implications for the potential role of HHV-6 in AIDS.",
author = "Paolo Lusso and Alfredo Garzino-Demo and Crowley, {Richard W.} and Malnati, {Mauro S.}",
year = "1995",
month = "4",
day = "1",
doi = "10.1084/jem.181.4.1303",
language = "English",
volume = "181",
pages = "1303--1310",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "4",

}

TY - JOUR

T1 - Infection of γ/δ T lymphocytes by human herpesvirus 6

T2 - Transcriptional induction of CD4 and susceptibility to HIV infection

AU - Lusso, Paolo

AU - Garzino-Demo, Alfredo

AU - Crowley, Richard W.

AU - Malnati, Mauro S.

PY - 1995/4/1

Y1 - 1995/4/1

N2 - Human herpesvirus 6 (HHV-6), a T-lymphotropic human herpesvirus, is a potentially immunosuppressive agent that has been suggested to play a role as a cofactor in the natural history of human immunodeficiency virus (HIV) infection. We studied the interactions between HHV-6 and γ/δ T lymphocytes, a subset of T cells involved in the protective immune response against specific microorganisms. Polyclonal γ/δ T cell populations, purified from the peripheral blood of healthy adults and activated in vitro with phytohemagglutinin, were exposed to HHV-6, strain GS (subgroup A), at the approximate multiplicity of infection (MOI) of 1. Signs of virus replication were detected as early as 72 h after infection, as documented by immunofluorescence, electron microscopy, and transmission of extracellular virus. Progression of the infection was associated with the appearance of typical cytomorphological changes and, eventually, massive cell death. In contrast, no signs of infection or cytopathic effects were detected after exposure of γ/δ T lymphocytes to HHV-7, a CD4+ T-lymphotropic virus closely related to HHV-6. Polyclonal γ/δ T cells displayed cytolytic activity against both autologous and heterologous target cells infected with HHV-6 and maintained this activity for at least 72 h after infection with HHV-6, despite the high MOI used. As previously documented in mature CD8+ α/β T cells and natural killer cells, HHV-6 infection induced γ/δ T lymphocytes to express de novo CD4 messenger RNA and protein, as detected by reverse transcriptase-polymerase chain reaction and fluorocytometry, respectively. Whereas purified CD4- γ/δ T cell populations were per se refractory to HIV infection, they became susceptible to productive infection by HIV-1, strain IIIB, after induction of CD4 expression by HHV-6. These results demonstrate that γ/δ T cells can be directly targeted and killed by a herpesvirus and may have implications for the potential role of HHV-6 in AIDS.

AB - Human herpesvirus 6 (HHV-6), a T-lymphotropic human herpesvirus, is a potentially immunosuppressive agent that has been suggested to play a role as a cofactor in the natural history of human immunodeficiency virus (HIV) infection. We studied the interactions between HHV-6 and γ/δ T lymphocytes, a subset of T cells involved in the protective immune response against specific microorganisms. Polyclonal γ/δ T cell populations, purified from the peripheral blood of healthy adults and activated in vitro with phytohemagglutinin, were exposed to HHV-6, strain GS (subgroup A), at the approximate multiplicity of infection (MOI) of 1. Signs of virus replication were detected as early as 72 h after infection, as documented by immunofluorescence, electron microscopy, and transmission of extracellular virus. Progression of the infection was associated with the appearance of typical cytomorphological changes and, eventually, massive cell death. In contrast, no signs of infection or cytopathic effects were detected after exposure of γ/δ T lymphocytes to HHV-7, a CD4+ T-lymphotropic virus closely related to HHV-6. Polyclonal γ/δ T cells displayed cytolytic activity against both autologous and heterologous target cells infected with HHV-6 and maintained this activity for at least 72 h after infection with HHV-6, despite the high MOI used. As previously documented in mature CD8+ α/β T cells and natural killer cells, HHV-6 infection induced γ/δ T lymphocytes to express de novo CD4 messenger RNA and protein, as detected by reverse transcriptase-polymerase chain reaction and fluorocytometry, respectively. Whereas purified CD4- γ/δ T cell populations were per se refractory to HIV infection, they became susceptible to productive infection by HIV-1, strain IIIB, after induction of CD4 expression by HHV-6. These results demonstrate that γ/δ T cells can be directly targeted and killed by a herpesvirus and may have implications for the potential role of HHV-6 in AIDS.

UR - http://www.scopus.com/inward/record.url?scp=0028986361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028986361&partnerID=8YFLogxK

U2 - 10.1084/jem.181.4.1303

DO - 10.1084/jem.181.4.1303

M3 - Article

C2 - 7699322

AN - SCOPUS:0028986361

VL - 181

SP - 1303

EP - 1310

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 4

ER -