Abstract
Open reading frame (ORF) 45 of Kaposi's sarcoma-associated herpesvirus (KSHV) is a tegument protein. A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress. In this study, ORF45 was found to interact with KIF3A, a kinesin-2 motor protein that transports cargoes along microtubules to cell periphery in a yeast two-hybrid screen. The association was confirmed by both co-immunoprecipitation and immunoflorescence approaches in primary effusion lymphoma cells following virus reactivation. ORF45 principally mediated the docking of entire viral capsid-tegument complexes onto the cargo-binding domain of KIF3A. Microtubules served as the major highways for transportation of these complexes as evidenced by drastically reduced viral titers upon treatment of cells with a microtubule depolymerizer, nocodazole. Confocal microscopic images further revealed close association of viral particles with microtubules. Inhibition of KIF3A–ORF45 interaction either by the use of a headless dominant negative (DN) mutant of KIF3A or through shRNA-mediated silencing of endogenous KIF3A expression noticeably decreased KSHV egress reflecting as appreciable reductions in the release of extracellular virions. Both these approaches, however, failed to impact HSV-1 egress, demonstrating the specificity of KIF3A in KSHV transportation. This study thus reports on transportation of KSHV viral complexes on microtubules by KIF3A, a kinesin motor thus far not implicated in virus transportation. All these findings shed light on the understudied but significant events in the KSHV life cycle, delineating a crucial role of a KSHV tegument protein in cellular transport of viral particles.
Highlights
Kaposi’s sarcoma–associated herpesvirus (KSHV), known as the human herpesvirus 8 (HHV-8), is a human DNA tumor virus [1]
Synthesized proteins assemble in an orderly fashion to form viral complexes that need to be transported to the cell periphery for release and to further infect fresh cells to maintain the infection
We show that a KSHV protein called the open reading frame (ORF) 45 anchors newly assembled viruses onto a cellular motor protein, namely KIF3A
Summary
Kaposi’s sarcoma–associated herpesvirus (KSHV), known as the human herpesvirus 8 (HHV-8), is a human DNA tumor virus [1]. KSHV infection of cells by default establishes latency During this phase, there is expression of only a limited number of the viral (latent) genes essential for maintenance of the viral genome with no production of infectious virions [4]. Disruption of latency results in the reactivation of the virus into the lytic phase, with expression of the entire viral gene panel and production of infectious viral particles [5,6]. These events ensure the propagation and transmission of viruses to uninfected cells serving to maintain the infection [7]. The KSHV lytic phase and constant primary infection of fresh cells is crucial for both the viral tumorigenicity and the disease pathogenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
