Rhesus macaque rhadinovirus-associated non-Hodgkin lymphoma

animal model for KSHV-associated malignancies

Beata U. Orzechowska, Michael F. Powers, Jerald Sprague, He Li, Bonnie Yen, Robert Searles, Michael Axthelm, Scott Wong

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Rhesus macaque rhadinovirus (RRV) is closely related to Kaposi sarcomaassociated herpesvirus (KSHV) and is associated with the development of B-cell hyperplasia and persistent lymphadenopathy resembling multicentric Castleman disease in rhesus macaques (RMs) coinfected with simian immunodeficiency virus (SIV). Here we investigated whether RMs experimentally infected with SIV and RRV can develop other disease manifestations observed in HIV- and KSHV-infected patients. As reported earlier, inoculation of SIV-infected RMs with RRV results in persistent RRV infection, whereas immunocompetent animals infected with RRV exhibit viremia 2 weeks after infection, followed by a period of no virus detection until they are subsequently made immunodeficient by SIV infection. A subset of animals developed abnormal cellular proliferations characterized as extranodal lymphoma and a proliferative mesenchymal lesion. In situ hybridization and immunohistochemistry analysis indicate RRV is present in both malignancies, and DNA microarray analysis detected viral interleukin-6 (vIL-6) and viral FLICE-like inhibitory protein (vFLIP) transcripts. Reverse-transcriptase polymerase chain reaction analysis confirmed vIL-6 and vFLIP expression, and that of RRV open reading frames 72 and 73, homologs of KSHV open reading frames shown to be expressed in primary effusion lymphoma. These data support the utility of the RRV-/ SIV-infected RM as an excellent animal model to investigate KSHV-like pathogenesis.

Original languageEnglish (US)
Pages (from-to)4227-4234
Number of pages8
JournalBlood
Volume112
Issue number10
DOIs
StatePublished - Nov 15 2008

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Rhadinovirus
Herpesviridae
Macaca mulatta
Viruses
Non-Hodgkin's Lymphoma
Animals
Animal Models
Simian Immunodeficiency Virus
Neoplasms
Interleukin-6
CASP8 and FADD-Like Apoptosis Regulating Protein
Polymerase chain reaction
RNA-Directed DNA Polymerase
Viral Proteins
Microarrays
Open Reading Frames
Proteins
Primary Effusion Lymphoma
Cells
Viremia

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Rhesus macaque rhadinovirus-associated non-Hodgkin lymphoma : animal model for KSHV-associated malignancies. / Orzechowska, Beata U.; Powers, Michael F.; Sprague, Jerald; Li, He; Yen, Bonnie; Searles, Robert; Axthelm, Michael; Wong, Scott.

In: Blood, Vol. 112, No. 10, 15.11.2008, p. 4227-4234.

Research output: Contribution to journalArticle

Orzechowska, Beata U. ; Powers, Michael F. ; Sprague, Jerald ; Li, He ; Yen, Bonnie ; Searles, Robert ; Axthelm, Michael ; Wong, Scott. / Rhesus macaque rhadinovirus-associated non-Hodgkin lymphoma : animal model for KSHV-associated malignancies. In: Blood. 2008 ; Vol. 112, No. 10. pp. 4227-4234.
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