TY - JOUR
T1 - Rhesus macaque rhadinovirus-associated non-Hodgkin lymphoma
T2 - animal model for KSHV-associated malignancies
AU - Orzechowska, Beata U.
AU - Powers, Michael F.
AU - Sprague, Jerald
AU - Li, He
AU - Yen, Bonnie
AU - Searles, Robert P.
AU - Axthelm, Michael K.
AU - Wong, Scott W.
PY - 2008/11/15
Y1 - 2008/11/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2008-04-151498
DO - 10.1182/blood-2008-04-151498
M3 - Article
C2 - 18757778
AN - SCOPUS:58149169170
SN - 0006-4971
VL - 112
SP - 4227
EP - 4234
JO - Blood
JF - Blood
IS - 10
ER -