Identification of Kaposi's sarcoma-associated herpesvirus (KSHV)-specific cytotoxic T-lymphocyte epitopes and evaluation of reconstitution of KSHV-specific responses in human immunodeficiency virus type 1-Infected patients receiving highly active antiretroviral therapy.
Following the introduction of highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) has significantly declined in human immunodeficiency virus type 1 (HIV-1)-positive (HIV-1(+)) individuals and clinical remission is often observed. We hypothesize that these effects are partly due to anti-KS-associated herpesvirus (KSHV) immune restoration. Here, 15-mer overlapping peptides from proteins K12 and K8.1 were used to identify novel KSHV-specific cytotoxic T-lymphocyte epitopes. Three immunogenic peptides, two lytic and one latent, were subsequently used to monitor the anti-KSHV CD8(+) T-cell responses in a cohort of 19 HIV-1(+) KSHV(+/-) KS(+/-) individuals during 52 weeks of HAART. KSHV and HIV-1 loads, KSHV antibody titers, and both CD4(+) and CD8(+) T-lymphocyte counts were enumerated. Prior to HAART, the total number of spot-forming cells (SFC) for all three peptides correlated with both CD4(+) and CD8(+) T-lymphocyte counts (P < or = 0.05) in the KSHV-positive KS-positive cohort (n = 11). Following 52 weeks of HAART, significant decreases in HIV-1 and KSHV loads were associated with significant increases in CD4(+) T-lymphocyte counts and number of SFC for the three KSHV-specific peptides. Although these increases were modest in comparison to the number of SFC observed with the HIV-1 gag peptide SLYNTVATL, they represented a fourfold increase from the baseline, continuing an upward trend to week 52.
Wilkinson
John
J
Department of Immunology, Chelsea and Westminster Hospital, Imperial College School of Medicine, London, United Kingdom.
Cope
Alethea
A
Gill
Jas
J
Bourboulia
Dimitra
D
Hayes
Peter
P
Imami
Nesrina
N
Kubo
Toru
T
Marcelin
Anne
A
Calvez
Vincent
V
Weiss
Robin
R
Gazzard
Brian
B
Boshoff
Chris
C
Gotch
Frances
F
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000821:virology; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification; D019288:Herpesvirus 8, Human / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D012514:Sarcoma, Kaposi / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D014764:Viral Proteins
D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; C113454:K8.1 protein, Human herpesvirus 8; D008565:Membrane Proteins; D010455:Peptides; C111200:SECTM1 protein, human; D014764:Viral Proteins