Impact of Kaposi sarcoma-associated herpesvirus (KSHV) burden and HIV coinfection on the detection of T cell responses to KSHV ORF73 and ORF65 proteins.
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.
Woodberry
Tonia
T
Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Suscovich
Todd J
TJ
Henry
Leah M
LM
Martin
Jeff N
JN
Dollard
Sheila
S
O'Connor
Paula G
PG
Davis
Jennifer K
JK
Osmond
Dennis
D
Lee
Tzong-Hae
TH
Kedes
Dean H
DH
Khatri
Ashok
A
Lee
Jeannette
J
Walker
Bruce D
BD
Scadden
David T
DT
Brander
Christian
C
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
D000956:Antigens, Viral; D036022:Capsid Proteins; D009687:Nuclear Proteins; C119019:ORF65 protein, human herpesvirus 8; D014764:Viral Proteins; C109540:latency-associated nuclear antigen