Human herpesvirus 6 variant A but not variant B induces fusion from without in a variety of human cells through a human herpesvirus 6 entry receptor, CD46.
Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus that productively infects T cells and monocytes. HHV-6 isolates can be differentiated into two groups, variants A and B (HHV-6A and HHV-6B). Here, we show a functional difference between HHV-6A and -6B in that HHV-6A induced syncytium formation of diverse human cells but HHV-6B did not. The syncytium formation induced by HHV-6A was observed 2 h after infection; moreover, it was found in the presence of cycloheximide, indicating that HHV-6A induced fusion from without (FFWO) in the target cells. Furthermore, the fusion event was dependent on the expression of the HHV-6 entry receptor, CD46, on the target cell membrane. In addition, we determined that short consensus repeat 2 (SCR2), -3, and -4 of the CD46 ectodomain were essential for the formation of the virus-induced syncytia. Monoclonal antibodies against glycoproteins B and H of HHV-6A inhibited the fusion event, indicating that the syncytium formation induced by HHV-6A required glycoproteins H and B. These findings suggest that FFWO, which HHV-6A induced in a variety of cell lines, may play an important role in the pathogenesis of HHV-6A, not only in lymphocytes but also in various tissues, because CD46 is expressed ubiquitously in human tissues.
Mori
Yasuko
Y
Department of Microbiology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. ymori@micro.med.osaka-u.ac.jp
Seya
Tsukasa
T
Huang
Hong Lan
HL
Akkapaiboon
Pilailuk
P
Dhepakson
Panadda
P
Yamanishi
Koichi
K
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002459:Cell Fusion; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D015726:Giant Cells / Q000502:physiology*; D015654:Herpesvirus 6, Human / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011991:Receptors, Virus / Q000378:metabolism*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism
D015703:Antigens, CD; C497857:CD46 protein, human; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C070917:glycoprotein H, herpesvirus 6