Mode of replication and pathogenicity of human herpesvirus 7

人类疱疹病毒7型（Human Herpesvirus 7，HHV-7）是一种新的嗜T淋巴细胞疱疹病毒，与人类疱疹病毒6型（Human Herpesvirus 6，HHV-6）有明显的区别。我们从健康成人的唾液样本中分离出几株临床分离株，经鉴定为HHV-7。建立了感染性滴定法和利用脐带血淋巴细胞获得高滴度无细胞病毒制剂的方法。比较分析了HHV-6A、6 B和7的一步生长曲线。在21个造血细胞系中，CD 4 + CD 8 + T细胞系SUP-T1是唯一支持HHV-7复制的细胞系。HHV-7在SUP-T1细胞中的病毒滴度与在脐血淋巴细胞中的病毒滴度相当，HHV-7感染SUP-T1细胞后可持续产生感染性病毒。培养物是感染细胞和未感染细胞的混合物，感染细胞的比例在10%至20%之间。在上清液中未检测到干扰素活性。然而，用外源性干扰素β处理培养物显著减少了病毒的产生，并治愈了持续感染的培养物。我们用SUP-T1细胞系和由SUP-T1建立的HIV携带者细胞系研究了HIV-1和HHV-7的相互作用。在HIV-1携带者细胞系中，CD 4抗原的表达完全下调。虽然HHV-6很容易重复感染HIV-1携带者SUP-T1细胞，但同样的细胞对HHV-7的重复感染完全耐受。此外，用抗CD 4单克隆抗体处理SUP-T1细胞可抑制HHV-7的生长。这些结果表明，HIV-1携带者SUP-T1细胞对HHV-7的抗性是由于细胞表面缺乏CD 4抗原，HIV-1和HHV-7使用相同的分子，即CD 4抗原作为病毒受体。

Human Herpesvirus 7 (HHV-7), a new T-lymphotropic herpesvirus, is related to, but significantly different from HHV-6. We isolated several clinical isolates from saliva samples of healthy adults, and they were identified as HHV-7. We established a method for infectious titration and a method to obtain high titer cell-free virus preparation using cord blood lymphocytes. One-step growth curves of HHV-6A,6B,and 7 were comparatively analyzed. Among 21 hematopoietic cell lines, a CD4+ CD8+ T cell line, SUP-T1, was the only cell line that supported HHV-7 replication. Virus titers of HHV-7 in SUP-T1 cells were comparable to those in cord blood lymphocytes.Persistent production of infectious virus was observed after infection of SUP-T1 cells with HHV-7. The culture was the mixture of infected and uninfected cells with the ratio of the infected cells ranging around 10 to 20%. Interferon activity was not detected in the supernatant. However, the treatment of the culture with exogenous interferon beta dramatically reduced the production of virus and cured the culture of the persistent infection. No virus production, infected cell, or HHV-7 genome was detectable.We studied the interaction of HIV-1 and HHV-7 using the SUP-T1 cell line and a HIV carrier cell line established from SUP-T1. Expression of the CD4 antigen was completely downregulated in the HIV-1 carrier cell line. While superinfection of HIV-1 carrier SUP-T1 cells with HHV-6 was readily accomplished, the same cells were completely resistant to superinfection with HHV-7. Furthermore, treatment of SUP-T1 cells with anti-CD4 monoclonal antibodies inhibited the growth of HHV-7. These results suggest that resistance of HIV-1 carrier SUP-T1 cells to HHV-7 is due to the absence of the CD4 antigen on the cell surface and that HIV-1 and HHV-7 use the same molecule, the CD4 antigen, as the virus receptor.