Down-regulation of CXCR4 by human herpesvirus 6 (HHV-6) and HHV-7.
Recent studies have demonstrated that human herpesvirus 6 (HHV-6) and HHV-7 interact with HIV-1 and alter the expression of various surface molecules and functions of T lymphocytes. The present study was undertaken to clarify whether coreceptors for HIV-1, CXCR4 and CCR5, are necessary for HHV-6 and HHV-7 infection. Although CXCR4 and CCR5 appeared not to be the coreceptors for these viruses, marked down-regulation of CXCR4, but not CCR5, was detected in HHV-6 variant A (HHV-6A)-, HHV-6 variant B (HHV-6B)-, and HHV-7-infected cells. Down-regulation of CXCR4 resulted in impairment of chemotaxis and a decreased level of elevation of the intracellular Ca2+ concentration in response to stromal cell-derived factor-1. Northern blot analysis of mRNAs extracted from HHV-6A-, HHV-6B-, and HHV-7-infected CD4+ T lymphocytes demonstrated a markedly decreased level of CXCR4 gene transcription, but the posttranscriptional stability of CXCR4 mRNA was not significantly altered. These data demonstrate that unlike HIV-1, HHV-6 and HHV-7 infections do not require expression of CXCR4 or CCR5, whereas marked down-regulation of CXCR4 is induced by these viruses, suggesting that HHV-6 and HHV-7 infections may render CD4+ T lymphocytes resistant to T lymphocyte-tropic HIV-1 infection.
Yasukawa
M
M
First Department of Internal Medicine, Ehime University School of Medicine, Japan. yasukawa@m.ehime-u.ac.jp
Hasegawa
A
A
Sakai
I
I
Ohminami
H
H
Arai
J
J
Kaneko
S
S
Yakushijin
Y
Y
Maeyama
K
K
Nakashima
H
H
Arakaki
R
R
Fujita
S
S
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D015536:Down-Regulation / Q000276:immunology*; D015654:Herpesvirus 6, Human / Q000502:physiology*; D016199:Herpesvirus 7, Human / Q000502:physiology*; D006801:Humans; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D000911:Antibodies, Monoclonal; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012333:RNA, Messenger; D019718:Receptors, CXCR4