3 years ago

Expression and subcellular localization of the KSHV K15P protein during latency and lytic reactivation in primary effusion lymphoma cells.

Wilson DW, Kharkwal H, Smith CG
The K15P membrane protein of Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with multiple cellular signaling pathways, and is thought to play key roles in KSHV-associated endothelial cell angiogenesis, regulation of B-cell receptor (BCR) signaling and the survival, activation and proliferation of BCR-negative primary effusion lymphoma (PEL) cells. Although full-length K15P is ∼45kDa in size, numerous lower molecular weight forms of the protein exist as a result of differential splicing and poorly characterized post-translational processing. K15P has been reported to localize to numerous subcellular organelles in heterologous expression studies, but there is limited data concerning the sorting of K15P in KSHV-infected cells. The relationship between the various molecular weight forms of K15P, their subcellular distribution and how these may differ in latent and lytic KSHV infections is poorly understood. Here we report that a cDNA encoding a full-length ∼45kDa K15P reporter protein is expressed as a ∼23/34kDa species that colocalizes with the trans Golgi network marker TGN46 in KSHV-infected PEL cells. Following lytic reactivation by sodium butyrate the levels of the ∼23-24kDa protein diminish and full-length ∼45kDa K15P accumulates. This is accompanied by apparent fragmentation of the TGN and redistribution of K15P to a dispersed peripheral location. Similar results were seen when lytic reactivation was stimulated by the KSHV replication and transcription activator (RTA), and during spontaneous reactivation. We speculate that expression of differing molecular weight forms of K15P, in distinct cellular locations, reflects the alternative demands placed upon the protein in the latent and lytic phases.IMPORTANCE The K15P protein of Kaposi's sarcoma-associated herpesvirus (KSHV) is thought to play key roles in disease, including KSHV-associated angiogenesis and the survival and growth of primary effusion lymphoma cells (PELs). The protein exists in multiple molecular weight forms and its intracellular trafficking is poorly understood. Here we demonstrate that the molecular weight form of a reporter K15P molecule, and its intracellular distribution, change when KSHV switches from its latent (quiescent) phase to the lytic, infectious state. We speculate that expression of differing molecular weight forms of K15P in distinct cellular locations reflects the alternative demands placed upon the protein in the viral latent and lytic stages.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28835496

DOI: PubMed:28835496

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.