title: Impact of Kaposi sarcoma-associated herpesvirus (KSHV) burden and HIV coinfection on the detection of T cell responses to KSHV ORF73 and ORF65 proteins.
abstract: Cellular immune responses to Kaposi sarcoma-associated herpesvirus (KSHV), the etiological agent of KS and several other malignancies, are incompletely characterized. We assessed KSHV-specific interferon- gamma enzyme-linked immunospot responses in a cohort of 154 individuals, using overlapping peptide sets spanning the KSHV-encoded latency-associated nuclear antigen (ORF73) and the minor capsid glycoprotein (ORF65). Among KSHV-seropositive subjects, ORF73-specific responses dominated over responses to ORF65 and were preferentially detected in human immunodeficiency virus-coinfected individuals who had elevated levels of cell-associated KSHV DNA, indicating that the viral antigen burden may have been driving these responses. Responses to both ORF73 and ORF65 were also detected in several KSHV-seronegative subjects who were at increased risk for KSHV infection, which demonstrates that cellular immunity can be found in the absence of detectable humoral responses. These data have implications for the reliable identification of KSHV infection and may help guide the design of immune-based therapeutic and prophylactic interventions.
authors: Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors: Tonia
authors: T
authors: Woodberry
authors: Todd J
authors: TJ
authors: Suscovich
authors: Leah M
authors: LM
authors: Henry
authors: Jeff N
authors: JN
authors: Martin
authors: Sheila
authors: S
authors: Dollard
authors: Paula G
authors: PG
authors: O'Connor
authors: Jennifer K
authors: JK
authors: Davis
authors: Dennis
authors: D
authors: Osmond
authors: Tzong-Hae
authors: TH
authors: Lee
authors: Dean H
authors: DH
authors: Kedes
authors: Ashok
authors: A
authors: Khatri
authors: Jeannette
authors: J
authors: Lee
authors: Bruce D
authors: BD
authors: Walker
authors: David T
authors: DT
authors: Scadden
authors: Christian
authors: C
authors: Brander
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D019288:Herpesvirus 8, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009687:Nuclear Proteins / Q000276:immunology; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D009687:Nuclear Proteins; C119019:ORF65 protein, human herpesvirus 8; D014764:Viral Proteins; C109540:latency-associated nuclear antigen