PMID- 10228019 OWN - NLM STAT- MEDLINE DCOM- 19990520 LR - 20071115 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 162 IP - 9 DP - 1999 May 1 TI - Down-regulation of CXCR4 by human herpesvirus 6 (HHV-6) and HHV-7. PG - 5417-22 AB - 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. FAU - Yasukawa, M AU - Yasukawa M AD - First Department of Internal Medicine, Ehime University School of Medicine, Japan. yasukawa@m.ehime-u.ac.jp FAU - Hasegawa, A AU - Hasegawa A FAU - Sakai, I AU - Sakai I FAU - Ohminami, H AU - Ohminami H FAU - Arai, J AU - Arai J FAU - Kaneko, S AU - Kaneko S FAU - Yakushijin, Y AU - Yakushijin Y FAU - Maeyama, K AU - Maeyama K FAU - Nakashima, H AU - Nakashima H FAU - Arakaki, R AU - Arakaki R FAU - Fujita, S AU - Fujita S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antibodies, Monoclonal) RN - 0 (CXCL12 protein, human) RN - 0 (Chemokine CXCL12) RN - 0 (Chemokines, CXC) RN - 0 (RNA, Messenger) RN - 0 (Receptors, CXCR4) SB - IM MH - Antibodies, Monoclonal/pharmacology MH - CD4-Positive T-Lymphocytes/immunology/metabolism/virology MH - Cell Movement/immunology MH - Cells, Cultured MH - Chemokine CXCL12 MH - Chemokines, CXC/physiology MH - Down-Regulation/*immunology MH - Herpesvirus 6, Human/*physiology MH - Herpesvirus 7, Human/*physiology MH - Humans MH - RNA, Messenger/antagonists & inhibitors/biosynthesis MH - Receptors, CXCR4/*antagonists & inhibitors/genetics/immunology MH - Virus Replication/immunology EDAT- 1999/05/05 00:00 MHDA- 1999/05/05 00:01 CRDT- 1999/05/05 00:00 PHST- 1999/05/05 00:00 [pubmed] PHST- 1999/05/05 00:01 [medline] PHST- 1999/05/05 00:00 [entrez] PST - ppublish SO - J Immunol. 1999 May 1;162(9):5417-22.