Pathogenic effects of human herpesvirus 6 in human lymphoid tissue ex vivo

Jean Charles Grivel, Fabio Santoro, Silvia Chen, Giovanni Fagá, Mauro S. Malnati, Yoshinori Ito, Leonid Margolis, Paolo Lusso

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Abstract

Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that has been suggested to act as a cofactor in the progression of human immunodeficiency virus disease. However, the lack of suitable experimental models has hampered the elucidation of the mechanisms of HHV-6-mediated immune suppression. Here, we used ex vivo lymphoid tissue to investigate the cellular tropism and pathogenic mechanisms of HHV-6. Viral strains belonging to both HHV-6 subgroups (A and B) were able to productively infect human tonsil tissue fragments in the absence of exogenous stimulation. The majority of viral antigen-expressing cells were CD4+ T lymphocytes expressing a nonnaive phenotype, while CD8+ T cells were efficiently infected only with HHV-6A. Accordingly, HHV-6A infection resulted in the depletion of both CD4+ and CD8+ T cells, whereas in HHV-6B-infected tissue CD4+ T cells were predominantly depleted. The expression of different cellular antigens was dramatically altered in HHV-6-infected tissues: whereas CD4 was upregulated, both CD46, which serves as a cellular receptor for HHV-6, and CD3 were downmodulated. However, CD3 downmodulation was restricted to infected cells, while the loss of CD46 expression was generalized. Moreover, HHV-6 infection markedly enhanced the production of the CC chemokine RANTES, whereas other cytokines and chemokines were only marginally affected. These results provide the first evidence, in a physiologically relevant study model, that HHV-6 can severely affect the physiology of secondary lymphoid organs through direct infection of T lymphocytes and modulation of key membrane receptors and chemokines.

Original languageEnglish
Pages (from-to)8280-8289
Number of pages10
JournalJournal of Virology
Volume77
Issue number15
DOIs
Publication statusPublished - 1 Aug 2003

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Grivel, J. C., Santoro, F., Chen, S., Fagá, G., Malnati, M. S., Ito, Y., Margolis, L., & Lusso, P. (2003). Pathogenic effects of human herpesvirus 6 in human lymphoid tissue ex vivo. Journal of Virology, 77(15), 8280-8289. https://doi.org/10.1128/JVI.77.15.8280-8289.2003