Abstract
RNA-binding proteins, particularly splicing factors, localize to sub-nuclear domains termed nuclear speckles. During certain viral infections, as the nucleus fills up with replicating virus compartments, host cell chromatin distribution changes, ending up condensed at the nuclear periphery. In this study we wished to determine the fate of nucleoplasmic RNA-binding proteins and nuclear speckles during the lytic cycle of the Kaposi’s sarcoma associated herpesvirus (KSHV). We found that nuclear speckles became fewer and dramatically larger, localizing at the nuclear periphery, adjacent to the marginalized chromatin. Enlarged nuclear speckles contained splicing factors, whereas other proteins were nucleoplasmically dispersed. Polyadenylated RNA, typically found in nuclear speckles under regular conditions, was also found in foci separated from nuclear speckles in infected cells. Poly(A) foci did not contain lncRNAs known to colocalize with nuclear speckles but contained the poly(A)-binding protein PABPN1. Examination of the localization of spliced viral RNAs revealed that some spliced transcripts could be detected within the nuclear speckles. Since splicing is required for the maturation of certain KSHV transcripts, we suggest that the infected cell does not dismantle nuclear speckles but rearranges their components at the nuclear periphery to possibly serve in splicing and transport of viral RNAs into the cytoplasm.
Highlights
Kaposi’s sarcoma-associated herpesvirus (KSHV), known as human herpesvirus 8 (HHV-8), is a member of the lymphotropic gammaherpesvirus subfamily and one of seven known oncogenic human viruses [1]
We aimed to determine the distribution of key RNA binding proteins (RBPs), which are often found in the nucleoplasm and in nuclear speckles known to contain many types of splicing factors, during the lytic KSHV infection cycle
Nuclear speckles are typically found in the nuclear interior, but in nuclei undergoing lytic infection, some of the nuclear speckles re-localized to the periphery of the nucleus adjacent to the condensed chromatin
Summary
Kaposi’s sarcoma-associated herpesvirus (KSHV), known as human herpesvirus 8 (HHV-8), is a member of the lymphotropic gammaherpesvirus subfamily and one of seven known oncogenic human viruses [1]. This obligatory parasite is the etiologic agent of Kaposi’s sarcoma (KS), an angioproliferative multifocal neoplasm of the skin and other organs, that predominantly occurs in immunodeficient individuals, such as AIDS patients, and among apparently healthy individuals, in particular the elderly. During latent infection the viral DNA exists in the cell nucleus in the form of a circular chromatinized episome, no new virions are produced and only a small proportion of
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