Construction of an infectious rhesus rhadinovirus bacterial artificial chromosome for the analysis of Kaposi's sarcoma-associated herpesvirus-related disease development

Ryan Estep, Michael F. Powers, Bonnie K. Yen, He Li, Scott Wong

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Rhesus rhadinovirus (RRV) is closely related to Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) and causes KSHV-like diseases in immunocompromised rhesus macaques (RM) that resemble KSHV-associated diseases including multicentric Castleman's disease and non-Hodgkin's lymphoma. RRV retains a majority of open reading frames (ORFs) postulated to be involved in the pathogenesis of KSHV and is the closest available animal model to KSHV infection in humans. Here we describe the generation of a recombinant clone of RRV strain 17577 (RRV17577) utilizing bacterial artificial chromosome (BAC) technology. Characterization of the RRV BAC demonstrated that it is a pathogenic molecular clone of RRV17577, producing virus that behaves like wild-type RRV both in vitro and in vivo. Specifically, BAC-derived RRV displays wild-type growth properties in vitro and readily infects simian immunodeficiency virus-infected RM, inducing B cell hyperplasia, persistent lymphadenopathy, and persistent infection in these animals. This RRV BAC will allow for rapid genetic manipulation of the RJlV genome, facilitating the creation of recombinant versions of RRV that harbor specific alterations and/or deletions of viral ORFs. This system will provide insights into the roles of specific RRV genes in various aspects of the viral life cycle and the RRV-associated pathogenesis in vivo in an RM model of infection. Furthermore, the generation of chimeric versions of RRV containing KSHV genes will allow analysis of the function and contributions of KSHV genes to viral pathogenesis by using a relevant primate model system.

Original languageEnglish (US)
Pages (from-to)2957-2969
Number of pages13
JournalJournal of Virology
Volume81
Issue number6
DOIs
StatePublished - Mar 2007

Fingerprint

Macacine herpesvirus 5
Rhadinovirus
Human herpesvirus 8
Bacterial Artificial Chromosomes
Human Herpesvirus 8
bacterial artificial chromosomes
cytogenetic analysis
Macaca mulatta
pathogenesis
Open Reading Frames
open reading frames
Clone Cells
animal models
clones
non-Hodgkin lymphoma
Simian immunodeficiency virus
Herpesviridae Infections
Simian Immunodeficiency Virus
lymphatic diseases
genes

ASJC Scopus subject areas

  • Immunology

Cite this

Construction of an infectious rhesus rhadinovirus bacterial artificial chromosome for the analysis of Kaposi's sarcoma-associated herpesvirus-related disease development. / Estep, Ryan; Powers, Michael F.; Yen, Bonnie K.; Li, He; Wong, Scott.

In: Journal of Virology, Vol. 81, No. 6, 03.2007, p. 2957-2969.

Research output: Contribution to journalArticle

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