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Journal of Virology, March 2002, p. 2634-2640, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2634-2640.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

John Wilkinson,1,2 Alethea Cope,3 Jas Gill,1,2 Dimitra Bourboulia,3 Peter Hayes,1,2 Nesrina Imami,1,2 Toru Kubo,1,2 Anne Marcelin,4 Vincent Calvez,4 Robin Weiss,3 Brian Gazzard,1,2 Chris Boshoff,3 and Frances Gotch1,2*

Departments of Immunology,1 HIV/GUM, Chelsea and Westminster Hospital, Imperial College School of Medicine,2 Wolfson Institute for Biomedical Research, University College London, London, United Kingdom,3 Hôpital Pitié-Salpetrière, Paris, France4

Received 19 July 2001/ Accepted 9 November 2001

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 <= 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.

* Corresponding author. Mailing address: Department of Immunology, Imperial College of Science, Technology, and Medicine, Chelsea and Westminster Hospital, 369 Fulham Rd., London SW10 9NH, United Kingdom. Phone: 44 (0)20 8746 5996. Fax: 44 (0)20 8746 5997. E-mail: f.gotch{at}ic.ac.uk.

Journal of Virology, March 2002, p. 2634-2640, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2634-2640.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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