Experimental transmission of Kaposi's sarcoma‐associated herpesvirus (KSHV/HHV‐8) to SIV‐positive and SIV‐negative rhesus macaques

Abstract:  Kaposi's sarcoma‐associated herpesvirus (KSHV) is a γ‐herpesvirus associated with Kaposi's sarcoma (KS) and two lymphoproliferative diseases, primary effusion lymphoma (PEL) and multicentric Castleman's disease. Studies on the biology and pathogenesis of KSHV have been limited by lack of efficient cell culture systems and lack of a suitable animal model for KS. Here we report on the experimental inoculation of SIV‐positive and SIV‐negative rhesus macaques with KSHV‐infected PEL cells or KSHV preparations derived from PEL cells. Low levels of viral DNA could be detected in cultivated peripheral blood mononuclear cell of all animals, as well as in the bone marrow of one monkey that died from SAIDS. However, we were not able to detect KSHV‐specific antibodies or transcripts, nor did we observe any symptoms clearly related to KSHV infection (e.g. KS or lympho‐proliferative disease). Hence, although KSHV replicates in rhesus macaques at very low levels, this non‐human primate host is unlikely to provide a useful animal model for disease.

[1]  Frederick Y. Wu,et al.  Spindle Cell Conversion by Kaposi's Sarcoma-Associated Herpesvirus: Formation of Colonies and Plaques with Mixed Lytic and Latent Gene Expression in Infected Primary Dermal Microvascular Endothelial Cell Cultures , 2001, Journal of Virology.

[2]  T. Schulz,et al.  Bone marrow failure associated with human herpesvirus 8 infection after transplantation. , 2000, The New England journal of medicine.

[3]  R. Desrosiers,et al.  The Primary Sequence of Rhesus Monkey Rhadinovirus Isolate 26-95: Sequence Similarities to Kaposi's Sarcoma-Associated Herpesvirus and Rhesus Monkey Rhadinovirus Isolate 17577 , 2000, Journal of Virology.

[4]  D. Dittmer,et al.  Inflammatory cytokines and the reactivation of Kaposi's sarcoma-associated herpesvirus lytic replication. , 2000, Virology.

[5]  J. McCune,et al.  Experimental Transmission of Kaposi's Sarcoma–Associated Herpesvirus (Kshv/Hhv-8) to Scid-Hu Thy/Liv Mice , 1999, The Journal of experimental medicine.

[6]  M. Axthelm,et al.  Induction of B Cell Hyperplasia in Simian Immunodeficiency Virus–Infected Rhesus Macaques with the Simian Homologue of Kaposi's Sarcoma–Associated Herpesvirus , 1999, The Journal of experimental medicine.

[7]  Lijun Wu,et al.  A Complex Translational Program Generates Multiple Novel Proteins from the Latently Expressed Kaposin (K12) Locus of Kaposi’s Sarcoma-Associated Herpesvirus , 1999, Journal of Virology.

[8]  E. van Marck,et al.  Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[9]  R. Searles,et al.  Sequence and Genomic Analysis of a Rhesus Macaque Rhadinovirus with Similarity to Kaposi’s Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 , 1999, Journal of Virology.

[10]  A. Schmidt,et al.  Activation in vivo of retroperitoneal fibromatosis-associated herpesvirus, a simian homologue of human herpesvirus-8. , 1999, The Journal of general virology.

[11]  D. Ganem,et al.  Limited Transmission of Kaposi’s Sarcoma-Associated Herpesvirus in Cultured Cells , 1998, Journal of Virology.

[12]  Jeffrey N. Martin,et al.  Sexual transmission and the natural history of human herpesvirus 8 infection. , 1998, The New England journal of medicine.

[13]  S. Topino,et al.  γ-Interferon Production in Peripheral Blood Mononuclear Cells and Tumor Infiltrating Lymphocytes From Kaposi's Sarcoma Patients: Correlation With the Presence of Human Herpesvirus-8 in Peripheral Blood Mononuclear Cells and Lesional Macrophages , 1998 .

[14]  R. Desrosiers,et al.  A herpesvirus of rhesus monkeys related to the human Kaposi's sarcoma-associated herpesvirus , 1997, Journal of virology.

[15]  D. Ganem KSHV and Kaposi's Sarcoma: The End of the Beginning? , 1997, Cell.

[16]  T. Rose,et al.  Identification of two homologs of the Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species , 1997, Journal of virology.

[17]  J. Böni,et al.  Simple monitoring of antiretroviral therapy with a signal‐amplification‐boosted HIV‐1 p24 antigen assay with heat‐denatured plasma , 1997, AIDS.

[18]  G. Nabel,et al.  Propagation of a human herpesvirus from AIDS-associated Kaposi's sarcoma. , 1997, The New England journal of medicine.

[19]  J. Russo,et al.  Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  E. Operskalski,et al.  The seroepidemiology of human herpesvirus 8 (Kaposi's sarcoma–associated herpesvirus): Distribution of infection in KS risk groups and evidence for sexual transmission , 1996, Nature Medicine.

[21]  J. Phair,et al.  KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma , 1996, Nature Medicine.

[22]  W. Zhong,et al.  Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. McGrath,et al.  Lytic growth of Kaposi's sarcoma–associated herpesvirus (human herpesvirus 8) in culture , 1996, Nature Medicine.

[24]  D R Hoover,et al.  Kaposi's sarcoma-associated herpesvirus infection prior to onset of Kaposi's sarcoma , 1996, AIDS.

[25]  C. Boshoff,et al.  Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma , 1995, The Lancet.

[26]  E. Cesarman,et al.  Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. , 1995, The New England journal of medicine.

[27]  E. Cesarman,et al.  Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. , 1994, Science.

[28]  R. Desrosiers,et al.  Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. , 1992, Science.

[29]  S. Topino,et al.  gamma-Interferon production in peripheral blood mononuclear cells and tumor infiltrating lymphocytes from Kaposi's sarcoma patients: correlation with the presence of human herpesvirus-8 in peripheral blood mononuclear cells and lesional macrophages. , 1998, Blood.

[30]  P. Luciw,et al.  Models for AIDS pathogenesis: simian immunodeficiency virus, simian-human immunodeficiency virus and feline immunodeficiency virus infections. , 1997, AIDS.