Rat Cytomegalovirus Virion-Associated Proteins R131 and R129 Are Necessary for Infection of Macrophages and Dendritic Cells

Abstract

Cytomegalovirus (CMV) establishes persistent, latent infection in hosts, causing diseases in immunocompromised patients, transplant recipients, and neonates. CMV infection modifies the host chemokine axis by modulating chemokine and chemokine receptor expression and by encoding putative chemokine and chemokine receptor homologues. The viral proteins have roles in cellular signaling, migration, and transformation, as well as viral dissemination, tropism, latency and reactivation. Herein, we review the contribution of CMV-encoded chemokines and chemokine receptors to these processes, and further elucidate the viral tropism role of rat CMV (RCMV) R129 and R131. These homologues of the human CMV (HCMV)-encoded chemokines UL128 and UL130 are of particular interest because of their dual role as chemokines and members of the pentameric entry complex, which is required for entry into cell types that are essential for viral transmission and dissemination. The contributions of UL128 and UL130 to acceleration of solid organ transplant chronic rejection are poorly understood, and are in need of an effective in vivo model system to elucidate the phenomenon. We demonstrated similar molecular entry requirements for R129 and R131 in the rat cells, as observed for HCMV, and provided evidence that R129 and R131 are part of the viral entry complex required for entry into macrophages, dendritic cells, and bone marrow cells.

Dissecting the cytomegalovirus CC chemokine: Chemokine activity and gHgLchemokine-dependent cell tropism are independent players in CMV infection

“…One way to study a herpesvirus protein in the context of an infection is to use a knockout virus. The predominant phenotype of infection of CC chemokine-negative CMV in cell culture is a restricted cell tropism [ 2 , 6 , 18 , 19 , 42 ]. In vivo studies with CC chemokine-negative viruses were predominantly done with MCMV [ 23 – 25 ], but also with RhCMV [ 43 , 44 ] and GPCMV [ 38 ].…”

Cytomegalovirus (CMV) Infection and Latency

“…Included in this collection are research articles that leverage novel in vivo model systems using rodent CMVs, which provide important insights to viral reactivation that extend beyond tissue culture studies. The strength of these systems allows investigators to assess viral dissemination [1], immunological responses [2], and the contribution of infection to the pathologies following transplant [3]-a major advancement to the field. In addition, the review articles in this Special Issue illuminate the important advances made by CMV investigators on the latent and reactivation phases of CMV infection [4][5][6][7].…”