Keith W. Jarosinski, PhD


Research Assistant Professor of Microbiology

Contact Information

Office: 3184 Medical Education and Research Facility
375 Newton Rd
Iowa City, IA 52242
Phone: 319-335-7789

Lab: 3166 Medical Education and Research Facility
375 Newton Rd
Iowa City, IA 52242
Phone: 319-335-3158

Email: keith-jarosinski@uiowa.edu


BS, Biotechnology, Rochester Institute of Technology
PhD, Microbiology, New York State Health Science Center

Post Doctorate, Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University

Research Summary

My laboratory is interested in the replication and pathogenesis of herpesviruses. We utilize the natural virus-host model of Marek's disease virus (MDV) in chickens. MDV causes Marek's disease, a devastating disease characterized by neurological disorders, generalized immune suppression, and neoplastic T cell lymphomas. The highly oncogenic nature of MDV makes this virus an excellent model for studying the transformation of lymphocytes and the metastasis of lymphoid tumors in animals and humans, in addition to its unique cell tropism and transmission traits. MDV initially infects B lymphocytes, followed by activated T lymphocytes, in which it can transform cells into lymphomas. Around 2 weeks after exposure to virus, MDV infects and replicates in feather follicle epithelium (FFE) cells in the skin where it is shed into the environment as dander. The infectious virus and dander is subsequently taken up through the respiratory tract of uninfected chickens and the virus life cycle is repeated within the new host.

Herpesvirus genes involved in latency and tumorigenesis

A unique feature of MDV is that its genome harbors two copies of its own telomerase RNA (TR) subunit, termed viral TR (vTR). TRs are an essential component of the telomerase enzyme responsible for elongating telomeres and thereby sustaining the life of the cell. The function vTR plays during MDV-induced tumorigenesis is a major focus of the laboratory.

MDV also contains two sets of tandem repeats within its genome that represent perfect telomeres. We have shown that MDV uses these telomeric repeats to integrate into the host's telomeres. Since herpesviruses often reactivate from latency, the ability to quickly reactivate to lytic infection during cellular stress would be highly beneficial. It is believed other herpesviruses may utilize a similar mechanism as some human herpesviruses also encode telomeric repeats.

Transmission of herpesviruses

How herpesviruses transmit from one host to the other is not well known. Our laboratory has identified two viral proteins, glycoprotein C (gC) and UL13 protein kinase, that are essential for transmission of MDV from chicken-to-chicken. The mechanistic role(s) these genes play during transmission is not known and projects are ongoing to better understand the functions these proteins play during herpesviral transmission.

Another focus in our laboratory is the evolutionary basis for host switching of herpesviruses. Herpesviruses are often associated with a single host species, indicating they have evolved together with their host over millions of years. For example, MDV spreads among chicken flocks with ease but does not often transmit to other avian species. Likewise, turkey herpesvirus (HVT) spreads among turkey flocks, but does not often transmit to other avian species. Despite a high level of homology between the two viruses, rarely do they jump species. Over the last decade, the occurrence of MDV transmitting to other avian species is increasing and this is troubling since MDV is oncogenic. Our goal is to understand how herpesviruses host switch and identify the genes responsible for this using natural virus-host models.

Herpesvirus replication

A unique attribute of MDV replication is its strict cell-associated nature during replication in tissue culture cells and during in vivo replication in lymphocytes. The only known cell type able to produce fully infectious virus are FFE cells in the skin. These characteristics are similar to the human herpesvirus varicella-zoster virus (VZV), which causes chicken pox and shingles, where fully infectious cell-free virus is only produced in skin cells. The reasons for why MDV and VZV are so tightly cell-associated in vitro have long been a hindrance to research on these viruses, but we intend to use this as a benefit to understanding herpesvirus replication.

Selected Publications

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Jarosinski K, Vautherot J.  Differential expression of Marek's disease virus (MDV) late proteins during in vitro and in situ replication: Role for pUL47 in regulation of the MDV UL46-UL49 gene locus.  Virology.  2015 October. 484:213-26.

Jarosinski K, Donovan K, Du G.  Expression of fluorescent proteins within the repeat long region of the Marek's disease virus genome allows direct identification of infected cells while retaining full pathogenicity.  Virus Res.  2015 April 2. 201:50-60.

Jarosinski K, Osterrieder N.  Marek's disease virus expresses multiple UL44 (gC) variants through mRNA splicing that are all required for efficient horizontal transmission.  J Virol.  2012 August. 86(15):7896-906.

Jarosinski K, Arndt S, Kaufer B, Osterrieder N.  Fluorescently tagged pUL47 of Marek's disease virus reveals differential tissue expression of the tegument protein in vivo.  J Virol.  2012 March. 86(5):2428-36.

Kaufer B, Arndt S, Trapp S, Osterrieder N, Jarosinski K.  Herpesvirus telomerase RNA (vTR) with a mutated template sequence abrogates herpesvirus-induced lymphomagenesis.  PLoS Pathog.  2011 October. 7(10):e1002333.

Kaufer B, Jarosinski K, Osterrieder N.  Herpesvirus telomeric repeats facilitate genomic integration into host telomeres and mobilization of viral DNA during reactivation.  J Exp Med.  2011 March 14. 208(3):605-15.

Kaufer B, Trapp S, Jarosinski K, Osterrieder N.  Herpesvirus telomerase RNA(vTR)-dependent lymphoma formation does not require interaction of vTR with telomerase reverse transcriptase (TERT).  PLoS Pathog.  2010 August 26. 6(8):e1001073.

Jarosinski K, Kattenhorn L, Kaufer B, Ploegh H, Osterrieder N.  A herpesvirus ubiquitin-specific protease is critical for efficient T cell lymphoma formation.  Proc Natl Acad Sci U S A.  2007 December 11. 104(50):20025-30.

Jarosinski K, Margulis N, Kamil J, Spatz S, Nair V, Osterrieder N.  Horizontal transmission of Marek's disease virus requires US2, the UL13 protein kinase, and gC.  J Virol.  2007 October. 81(19):10575-87.

Jarosinski K, Osterrieder N, Nair V, Schat K.  Attenuation of Marek's disease virus by deletion of open reading frame RLORF4 but not RLORF5a.  J Virol.  2005 September. 79(18):11647-59.

Date Last Modified: 06/06/2016 - 13:17:48