Kaposi’s sarcoma-associated herpesvirus (KSHV) is one of the few oncogenic human viruses known to date. Its large genome encodes more than 85 proteins and includes both unique viral proteins as well as proteins conserved amongst herpesviruses. KSHV ORF20 is a member of the herpesviral core UL24 family, but the function of ORF20 and its role in the viral life cycle is not well understood. ORF20 encodes three largely uncharacterized isoforms, which we found were localized predominantly in the nuclei and nucleoli. Quantitative affinity purification coupled to mass spectrometry (q-AP-MS) identified numerous specific interacting partners of ORF20, including ribosomal proteins and the interferon-stimulated gene product (ISG) oligoadenylate synthetase-like protein (OASL). Both endogenous and transiently transfected OASL co-immunoprecipitated with ORF20, and this interaction was conserved among all ORF20 isoforms and multiple ORF20 homologs of the UL24 family in other herpesviruses. Characterization of OASL interacting partners by q-AP-MS identified a very similar interactome to that of ORF20. Both ORF20 and OASL copurified with 40S and 60S ribosomal subunits, and when they were co-expressed, they associated with polysomes. Although ORF20 did not have a global effect on translation, ORF20 enhanced RIG-I induced expression of endogenous OASL in an IRF3-dependent but IFNAR-independent manner. OASL has been characterized as an ISG with antiviral activity against some viruses, but its role for gammaherpesviruses was unknown. We show that OASL and ORF20 mRNA expression were induced early after reactivation of latently infected HuARLT-rKSHV.219 cells. Intriguingly, we found that OASL enhanced infection of KSHV. During infection with a KSHV ORF20stop mutant, however, OASL-dependent enhancement of infectivity was lost. Our data have characterized the interaction of ORF20 with OASL and suggest ORF20 usurps the function of OASL to benefit KSHV infection. The herpesviruses are a family of large double-stranded DNA viruses that cause a variety of illnesses from chicken pox to cancer. Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-causing herpesvirus and can lead to development of Kaposi’s sarcoma, a major form of cancer in HIV-positive patients. As for all herpesviruses, infection with KSHV is lifelong. Exactly how KSHV initiates and maintains its infection is still not well understood, but it must manipulate the host cell to establish favorable conditions. Likewise, the host has developed a complicated system to fight off invaders, which includes the production of interferon-stimulated gene products. We have now found that KSHV exploits one such host cell protein, the oligoadenylate synthetase-like protein (OASL). Rather than OASL acting as an antiviral protein as it does during many other viral infections, KSHV appears to have found a way to utilize OASL for its own benefit. The KSHV protein ORF20 interacts with OASL, they co-localize in nucleoli, and both ORF20 and OASL associate and purify with components of the cellular translational machinery. This may help viral infection by selectively controlling protein production.

Nuclear mRNA export is a highly complex and regulated process in cells. Cellular transcripts must undergo successful maturation processes, including splicing, 5'-, and 3'-end processing, which are essential for assembly of an export competent ribonucleoprotein particle. Many viruses replicate in the nucleus of the host cell and require cellular mRNA export factors to efficiently export viral transcripts. However, some viral mRNAs undergo aberrant mRNA processing, thus prompting the viruses to express their own specific mRNA export proteins to facilitate efficient export of viral transcripts and allowing translation in the cytoplasm. This review will focus on the Kaposi’s sarcoma-associated herpesvirus ORF57 protein, a multifunctional protein involved in all stages of viral mRNA processing and that is essential for virus replication. Using the example of ORF57, we will describe cellular bulk mRNA export pathways and highlight their distinct features, before exploring how the virus has evolved to exploit these mechanisms.

Previous studies have shown that autistic people often display atypical responses when processing sensory information, with particular prevalence within the auditory domain. Often provoked by common everyday sounds, auditory hypersensitivity can result in self-regulatory fear responses. This can be potentially harmful to autistic individuals and the people around them and is associated with greater occurrence of anxiety, depression, and poorer overall quality of life in the autistic population. Rather than a physiological causation, the literature suggests that hypersensitivity to sound is likely to be caused by how auditory stimuli are processed in the brain. This paper reports a home-based digital intervention aimed to address auditory hypersensitivity in autistic children. Developed as an interactive virtual reality game, the system integrates exposure-based therapy techniques into game mechanics and delivers target auditory stimuli to the player rendered via binaural-based spatial audio. The performance of the platform was evaluated in a 10-week feasibility study, during which children (n = 7) engaged weekly with the game during a 30 min session. Following this period, a comparison of pre- and post-study measurements showed a decrease in sensitivity for five participants, with qualitative feedback highlighting an increase in tolerance towards real-world stimuli and challenging environments. These results provide initial support for SoundFields as a home-based intervention targeting auditory hypersensitivity experienced by autistic children.

The coupling of mRNA processing steps is essential for precise and efficient gene expression. The human transcription/export (hTREX) complex is a highly conserved multi-protein complex responsible for eukaryotic mRNA stability and nuclear export. We have previously shown that the Kaposi's sarcoma-associated ORF57 protein orchestrates the recruitment of the hTREX complex onto viral intronless mRNA forming a stable and export competent viral ribonucleoprotein particle (vRNP). Recently, additional cellular proteins, namely CHTOP, CIP29 and POLDIP3 have been proposed as novel hTREX components. Herein we extend our previous research and provide evidence that ORF57 interacts with CHTOP and CIP29, in contrast to POLDIP3. Moreover, depletion studies show both CHTOP and CIP29 effect ORF57-mediated viral mRNA processing. As such, these results suggest both CHTOP and CIP29 are hTREX components and are recruited to an ORF57-mediated vRNP.

The γ‑herpesviruses Epstein-Barr virus and Kaposi's sarcoma‑associated herpesvirus are successful pathogens, each infecting a large proportion of the human population. These viruses persist for the life of the host and may each contribute to a number of malignancies, for which there are currently no cures. Large‑scale proteomic-based approaches provide an excellent means of increasing the collective understanding of the proteomes of these complex viruses and elucidating their numerous interactions within the infected host cell. These large‑scale studies are important for the identification of the intricacies of viral infection and the development of novel therapeutics against these two important pathogens.