1887

Abstract

Two distinct lineages of rhadinoviruses related to Kaposi's sarcoma (KS)-associated herpesvirus (KSHV; ), the causative agent of KS, have been identified. In macaques, the RV1 lineage is represented by retroperitoneal fibromatosis (RF) herpesvirus (RFHV), the homologue of KSHV, whilst the RV2 lineage is represented by rhesus rhadinovirus (RRV), a more distantly related virus. Real-time quantitative PCR was used to estimate the loads of RV1 and RV2 rhadinoviruses in simian acquired immunodeficiency syndrome-associated RF (SAIDS-RF), a neoplasm of macaques with similarities to AIDS-associated KS. Both RV1 and RV2 rhadinoviruses were detected in macaques with RF. The RV1 loads were 220- to 4300-fold higher in RF tumours than in spleen, showing a strong tumour association (mean loads of 1 800 000 vs 2900 copies per 10 cells in tumours and spleen, respectively). In contrast, RV2 loads in the RF tumours were 100-fold lower than RV1 loads and showed similar levels in tumours and spleen (mean loads of 16 000 vs 24 000 copies per 10 cells, respectively). Immunostaining with antibodies reactive against RFHV ORF73 latency-associated nuclear antigen (LANA) showed intense nuclear staining of the spindleoid RF tumour cells. Correlation of viral load and the number of LANA-positive cells indicated that RF tumour cells contained multiple copies of the RFHV genome per cell. This pattern of infectivity is similar to that seen in KS tumours latently infected with KSHV. Our study demonstrates similarities in the biology of KSHV and RFHV and supports a role for RFHV in the aetiology of SAIDS-RF.

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2006-12-01
2024-04-26
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References

  1. Alexander L., Denekamp L., Knapp A., Auerbach M. R., Damania B., Desrosiers R. C. 2000; The primary sequence of rhesus monkey rhadinovirus isolate 26-95: sequence similarities to Kaposi's sarcoma-associated herpesvirus and rhesus monkey rhadinovirus isolate 17577. J Virol 74:3388–3398 [CrossRef]
    [Google Scholar]
  2. Auerbach M. R., Czajak S. C., Johnson W. E., Desrosiers R. C., Alexander L. 2000; Species specificity of macaque rhadinovirus glycoprotein B sequences. J Virol 74:584–590 [CrossRef]
    [Google Scholar]
  3. Benveniste R. E., Stromberg K., Morton W. R., Giddens W. E., Jr. 1986; Association of retroperitoneal fibromatosis with type D retroviruses. In Animal Models of Retrovirus Infection and their Relationship to AIDS pp  335–353 Edited by Salzman L. A. San Diego: Academic Press;
    [Google Scholar]
  4. Bergquam E. P., Avery N., Shiigi S. M., Axthelm M. K., Wong S. W. 1999; Rhesus rhadinovirus establishes a latent infection in B lymphocytes in vivo. J Virol 73:7874–7876
    [Google Scholar]
  5. Bielefeldt-Ohmann H., Barouch D. H., Bakke A. M. & 8 other authors 2005; Intestinal stromal tumors in a simian immunodeficiency virus-infected, simian retrovirus-2 negative rhesus macaque ( Macaca mulatta ). Vet Pathol 42:391–396 [CrossRef]
    [Google Scholar]
  6. Boshoff C., Weiss R. A. 2001; Epidemiology and pathogenesis of Kaposi's sarcoma-associated herpesvirus. Philos Trans R Soc Lond B Biol Sci 356:517–534 [CrossRef]
    [Google Scholar]
  7. Boshoff C., Schulz T. F., Kennedy M. M., Graham A. K., Fisher C., Thomas A., McGee J. O., Weiss R. A., O'Leary J. J. 1995; Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med 1:1274–1278 [CrossRef]
    [Google Scholar]
  8. Bruce A. G., Bakke A. M., Thouless M. E., Rose T. M. 2005; Development of a real-time QPCR assay for the detection of RV2 lineage-specific rhadinoviruses in macaques and baboons. Virol J 2:2 [CrossRef]
    [Google Scholar]
  9. Burnside K. L., Ryan J. T., Bielefeldt-Ohmann H., Bruce A. G., Thouless M. E., Tsai C.-C., Rose T. M. 2006; RFHVMn ORF73 is structurally related to the KSHV ORF73 latency-associated nuclear antigen (LANA) and is expressed in retroperitoneal fibromatosis (RF) tumor cells. Virology 354:103–115 [CrossRef]
    [Google Scholar]
  10. Cesarman E., Chang Y., Moore P. S., Said J. W., Knowles D. M. 1995; Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 332:1186–1191 [CrossRef]
    [Google Scholar]
  11. Chang Y., Cesarman E., Pessin M. S., Lee F., Culpepper J., Knowles D. M., Moore P. S. 1994; Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266:1865–1869 [CrossRef]
    [Google Scholar]
  12. Desrosiers R. C., Sasseville V. G., Czajak S. C., Zhang X., Mansfield K. G., Kaur A., Johnson R. P., Lackner A. A., Jung J. U. 1997; A herpesvirus of rhesus monkeys related to the human Kaposi's sarcoma-associated herpesvirus. J Virol 71:9764–9769
    [Google Scholar]
  13. Giddens W. E. Jr, Tsai C. C., Morton W. R., Ochs H. D., Knitter G. H., Blakley G. A. 1985; Retroperitoneal fibromatosis and acquired immunodeficiency syndrome in macaques. Pathologic observations and transmission studies. Am J Pathol 119:253–263
    [Google Scholar]
  14. Greensill J., Schulz T. F. 2000; Rhadinoviruses (gamma2-herpesviruses) of Old World primates: models for KSHV/HHV8-associated disease?. AIDS 14 (Suppl. 3):S11–S19 [CrossRef]
    [Google Scholar]
  15. Greensill J., Sheldon J. A., Renwick N. M., Beer B. E., Norley S., Goudsmit J., Schulz T. F. 2000; Two distinct gamma-2 herpesviruses in African green monkeys: a second gamma-2 herpesvirus lineage among old world primates?. J Virol 74:1572–1577 [CrossRef]
    [Google Scholar]
  16. Kedes D. H., Lagunoff M., Renne R., Ganem D. 1997; Identification of the gene encoding the major latency-associated nuclear antigen of the Kaposi's sarcoma-associated herpesvirus. J Clin Invest 100:2606–2610 [CrossRef]
    [Google Scholar]
  17. Kellam P., Bourboulia D., Dupin N., Shotton C., Fisher C., Talbot S., Boshoff C., Weiss R. A. 1999; Characterization of monoclonal antibodies raised against the latent nuclear antigen of human herpesvirus 8. J Virol 73:5149–5155
    [Google Scholar]
  18. Lacoste V., Kadyrova E., Chistiakova I., Gurtsevitch V., Judde J. G., Gessain A. 2000a; Molecular characterization of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 strains from Russia. J Gen Virol 81:1217–1222
    [Google Scholar]
  19. Lacoste V., Mauclère P., Dubreuil G., Lewis J., Georges-Courbot M.-C., Gessain A. 2000b; KSHV-like herpesviruses in chimps and gorillas. Nature 407:151–152 [CrossRef]
    [Google Scholar]
  20. Lacoste V., Mauclère P., Dubreuil G., Lewis J., Georges-Courbot M.-C., Rigoulet J., Petit T., Gessain A. 2000c; Simian homologues of human gamma-2 and betaherpesviruses in mandrill and drill monkeys. J Virol 74:11993–11999 [CrossRef]
    [Google Scholar]
  21. Lacoste V., Mauclère P., Dubreuil G., Lewis J., Georges-Courbot M.-C., Gessain A. 2001; A novel gamma 2-herpesvirus of the rhadinovirus 2 lineage in chimpanzees. Genome Res 11:1511–1519 [CrossRef]
    [Google Scholar]
  22. London W. T., Sever J. L., Madden D. L. 7 other authors 1983; Experimental transmission of simian acquired immunodeficiency syndrome (SAIDS) and Kaposi-like skin lesions. Lancet 2:869–873
    [Google Scholar]
  23. Marx P. A., Lowenstine L. J. 1987; Mesenchymal neoplasms associated with type D retroviruses in macaques. Cancer Surv 6:101–115
    [Google Scholar]
  24. Marx P. A., Bryant M. L., Osborn K. G. & 18 other authors 1985; Isolation of a new serotype of simian acquired immune deficiency syndrome type D retrovirus from Celebes black macaques ( Macaca nigra ) with immune deficiency and retroperitoneal fibromatosis. J Virol 56:571–578
    [Google Scholar]
  25. Rainbow L., Platt G. M., Simpson G. R., Sarid R., Gao S.-J., Stoiber H., Herrington C. S., Moore P. S., Schulz T. F. 1997; The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen. J Virol 71:5915–5921
    [Google Scholar]
  26. Rose T. M., Strand K. B., Schultz E. R., Schaefer G., Rankin G. W. Jr, Thouless M. E., Tsai C.-C., Bosch M. L. 1997; Identification of two homologs of the Kaposi's sarcoma-associated herpesvirus (Human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species. J Virol 71:4138–4144
    [Google Scholar]
  27. Rose T. M., Schultz E. R., Henikoff J. G., Pietrokovski S., McCallum C. M., Henikoff S. 1998; Consensus-degenerate hybrid oligonucleotide primers for amplification of distantly related sequences. Nucleic Acids Res 26:1628–1635 [CrossRef]
    [Google Scholar]
  28. Rose T. M., Ryan J. T., Schultz E. R., Raden B. W., Tsai C.-C. 2003; Analysis of 4.3 kilobases of the divergent locus B of macaque retroperitoneal fibromatosis-associated herpesvirus reveals a close similarity in gene sequence and genome organization to Kaposi's sarcoma-associated herpesvirus. J Virol 77:5084–5097 [CrossRef]
    [Google Scholar]
  29. Russo J. J., Bohenzky R. A., Chien M.-C. & 8 other authors 1996; Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A 93:14862–14867 [CrossRef]
    [Google Scholar]
  30. Schultz E. R., Rankin G. W. Jr, Blanc M.-P., Raden B. W., Tsai C.-C., Rose T. M. 2000; Characterization of two divergent lineages of macaque rhadinoviruses related to Kaposi's sarcoma-associated herpesvirus. J Virol 74:4919–4928 [CrossRef]
    [Google Scholar]
  31. Searles R. P., Bergquam E. P., Axthelm M. K., Wong S. W. 1999; Sequence and genomic analysis of a Rhesus macaque rhadinovirus with similarity to Kaposi's sarcoma-associated herpesvirus/Human herpesvirus 8. J Virol 73:3040–3053
    [Google Scholar]
  32. Shibata R., Maldarelli F., Siemon C., Matano T., Parta M., Miller G., Fredrickson T., Martin M. A. 1997; Infection and pathogenicity of chimeric simian–human immunodeficiency viruses in macaques: determinants of high virus loads and CD4 cell killing. J Infect Dis 176:362–373 [CrossRef]
    [Google Scholar]
  33. Shiigi S. M., Wilson B. J., Malley A., Chandler R. A., Howard C. F. Jr, Olson L. C., Palotay J. L., McNulty W. P., Marx P. A. 1986; Association of SAIDS/RF-related signs with current or past SAIDS type 2 retrovirus infection in a colony of Celebes black macaques. Lab Anim Sci 36:20–23
    [Google Scholar]
  34. Soulier J., Grollet L., Oksenhendler E. & 8 other authors 1995; Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86:1276–1280
    [Google Scholar]
  35. Tsai C.-C. 1993; Fibromatosis in macaques infected with type D retroviruses. In Monographs on Pathology of Laboratory Animals: Nonhuman Primates I pp  48–57 Edited by Jones T. C., Mohr U., Hunt R. D. New York: Springer-Verlag;
    [Google Scholar]
  36. Tsai C.-C., Warner T. F., Uno H., Giddens W. E. Jr, Ochs H. D. 1985; Subcutaneous fibromatosis associated with an acquired immune deficiency syndrome in pig-tailed macaques. Am J Pathol 120:30–37
    [Google Scholar]
  37. Wang Y., Thouless M. E. 1996; Use of polymerase chain reaction for diagnosis of type D simian retrovirus infection in macaque blood. Lab Anim Sci 46:187–192
    [Google Scholar]
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