Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins

Human herpesvirus 8 (HHV-8) is a recently discovered gammaherpesvirus that is the etiologic agent of Kaposi sarcoma (KS). The natural history of prima ry HHV-8 infection, including clinical outcome and host immune responses th at may be important in preventing disease related to HHV-8, has not been el ucidated. The present study characterized the clinical, immunologic, and vi rologic parameters of primary HHV-8 infection in 5 cases detected during a 15-year longitudinal study of 108 human immunodeficiency virus type 1 seron egative men in the Multicenter AIDS Cohort Study. Primary HHV-8 infection w as associated with mild, nonspecific signs and symptoms of diarrhea, fatigu e, localized rash, and lymphadenopathy. There were no alterations in number s of CD4(+) or CD8(+) T cells or CD8(+) T-cell interferon gamma (IFN-(gamma )) production to mitogen or nominal antigen. CD8+ cytotoxic T-lymphocyte pr ecursor (CTLp) and IFN-gamma reactivity were detected during primary HHV-8 infection, with broad specificity to 5 lytic cycle proteins of HHV-8 encode d by open reading frame 8 (ORF 8; glycoprotein B homolog of Epstein-Barr vi rus), ORF 22 (gH homolog), ORF 25 (major capsid protein homolog), ORF 26 (a minor capsid protein homolog), or ORF 57 (an early protein homolog), in as sociation with increases in serum antibody titers and appearance of HHV-8 D NA in blood mononuclear cells. CD8+ T-cell responses to HHV-8 decreased by 2 to 3 years after primary infection. This antiviral T-cell response may co ntrol initial HHV-8 infection and prevent development of disease. (Blood. 2 001;97:2366-2373) (C) 2001 by The American Society of Hematology.