Jpn. J. Infect. Dis., 53, 137-155, 2000

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Review

Human Herpesvirus 8--Virology, Epidemiology and Related Diseases--

Harutaka Katano* and Tetsutaro Sata

Department of Pathology, National Institute of Infectious Diseases,
Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan

(Received June 22, 2000. Accepted July 31, 2000)

CONTENTS:
Summary
1. Introduction
2. Virology 
 2.1 Classification
 2.2 Virion morphology
 2.3 Genome structure and gene expression
   2.3.1 Immediate-early genes
   2.3.2 Early genes
   2.3.3 Late genes
   2.3.4 Latent genes 
 2.4 HHV-8-encoded cytokines and oncoproteins
   2.4.1 Viral cytokines
   2.4.2 Viral oncoproteins
 2.5 Experimental infection in vitro
3. Diagnosis of HHV-8 infection
 3.1 PCR
 3.2 Histological detection of HHV-8
 3.3 Serology
4. Epidemiology
 4.1 Seroprevalence and transmission
 4.2 Molecular epidemiology
5. HHV-8 related diseases
 5.1 Kaposi's sarcoma
 5.2 Primary effusion lymphoma
 5.3 Multicentric Castleman's disease 
 5.4 AIDS-associated anaplastic large cell lymphoma
 5.5 Others
6. Conclusion

SUMMARY: Human herpesvirus 8 ([HHV-8], Kaposi's sarcoma-associated herpesvirus [KSHV]) is a novel human oncovirus classified as a gamma-herpesvirus. HHV-8 is associated with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and some cases of multicentric Castleman's disease (MCD). Antibodies against HHV-8 are detected in the sera of almost all KS patients, about 30% of HIV-infected homosexual males in the world and 1.4% of the Japanese population. In HHV-8-associated malignancies such as KS and PEL, HHV-8 latently infects these tumor cells. Unlike other viruses, HHV-8 encodes several human homologues including cytokines (IL-6, MIPs, IRFs) and regulatory proteins (cyclin D, G-protein coupled receptor [GPCR]). These proteins may play significant roles in the pathogenesis of HHV-8-associated diseases. It has been demonstrated in vitro that the functions of retinoblastoma and p53 proteins were inhibited by viral cyclin D and latency-associated nuclear antigen, respectively. Mice transgenic for GPCR have a KS-like region in the skin. These data suggest the full oncogenecity of HHV-8. On the other hand, many cells expressing lytic proteins are found in MCD tissues, suggesting that the pathogenesis of MCD is different from that of HHV-8-associated malignancies.

*Corresponding author: Tel: +81-3-5285-1111 ext. 2627, Fax: +81-3-5285-1189, E-mail: katano@nih.go.jp

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