AEGiS-11IAC: Characterization of the DNA polymerase and glycoprotein B genes of Kaposi's sarcoma-associated and related herpesviruses.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Characterization of the DNA polymerase and glycoprotein B genes of Kaposi's sarcoma-associated and related herpesviruses.

Int Conf AIDS 1996 Jul 7-12; 11:7 (abstract no. We.A.161)
Bennett J, Strand K, Schultz E, Bosch M, Tsai CC, Schaefer G, Rose TM; Dept. Pathobiology, University of Washington, Seattle, WA. E-mail: trose@u.washington.edu.

OBJECTIVES: To identify and characterize potential therapeutic, diagnostic and vaccine targets for Kaposi's sarcoma and other AIDS-related malignancies.

METHODS: DNA was isolated from Kaposi's sarcoma (KS) lesions of patients with AIDS and retroperitoneal fibromatosis (RF) lesions of Macaca nemistrina with simian AIDS (SAIDS). Highly sensitive polymerase chain reaction (PCR) assays were performed using degenerate oligonucleotide primers designed against regions of the DNA polymerase (POL) and glycoprotein B (GLYB) genes which are highly conserved within the family of herpesviruses. Amplified DNA fragments were cloned, and the nucleotide and encoded amino acid sequences were determined. Computer homology analyses were done to identify the isolated DNA fragments.

RESULTS: DNA fragments containing sequences corresponding to herpesvirus-like POL and GLYB genes were identified in KS and RF lesions. The POL-like fragments from KS and RF were identical at 71% of the nucleotides and 84% of the encoded amino acids while the GLYB-like fragments were identical at 76% nucleotides and 90% of the encoded amino acids. A comparison of these sequences with the comparable genes from other herpesviruses demonstrated a higher sequence similarity to gamma herpesviruses including EBV than to members of the alpha or beta herpesvirus subclasses. The similarity of the KS and RF POL fragments with EBV POL was 62-66% (nucleotide) and 62-63% (amino acid), while the similarity of the KS and RF GLYB fragments with EBV GLYB was 49-52% (nucleotide) and 40% (amino acid).

CONCLUSIONS: We have identified herpesvirus-like POL and GLYB sequences in KS lesions which confirms previous studies of others who detected and characterized a new herpesvirus associated with KS (KSHV or human herpesvirus 8 (HV8)). Our sequences are predicted to comprise additional regions of the human HV8 genome. We have also identified similar sequences in a putative macaque homolog of HV8. The strong similarity between the encoded GLYB sequences of the HV8 homologs and the weak similarity between these sequences and the GLYB sequences of other herpesviruses indicates that the GLYB sequences would be suitable targets for viral specific serological assays or vaccine therapeutics. The strong sequence similarity between the POL genes of human and macaque HV8 suggest that therapeutic drugs targeting replication of HV8 in KS could be developed in the macaque RF model.

Keywords: AEGIS, Sarcoma, Kaposi, Herpesviridae, Herpesvirus 8, Human, DNA-Directed DNA Polymerase, Acquired Immunodeficiency Syndrome, Herpesviridae Infections, Herpesvirus 4, Human, Polymerase Chain Reaction, Macaca, Glycoproteins, Simplexvirus, Virus Replication, DNA Primers, Animal, Human, virology, ICA11

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