Microbiology

Keith W. Jarosinski, PhD

Portrait

Research Assistant Professor of Microbiology

Contact Information

Office: 3184 Medical Education and Research Facility
375 Newton Rd
Iowa City, IA 52242
Office 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

Education

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

Post Doctoral, Avian Unit, 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.

All Publications

Shaikh S, Katneni U, Dong H, Gaddamanugu S, Tavlarides-Hontz P, Jarosinski K, Osterrieder N, Parcells M.  A deletion in the glycoprotein L (gL) gene of U.S. Marek's disease virus (MDV) field strains is insufficient to confer increased pathogenicity to the bacterial artificial chromosome (BAC)-based strain, RB-1B.  Avian Dis.  2013 June. 57(2 Suppl):509-18.
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Schat K, Piepenbrink M, Buckles E, Schukken Y, Jarosinski K.  Importance of differential expression of Marek's disease virus gene pp38 for the pathogenesis of Marek's disease.  Avian Dis.  2013 June. 57(2 Suppl):503-8.
[Link]

Veiga I, Jarosinski K, Kaufer B, Osterrieder N.  Marek's disease virus (MDV) ubiquitin-specific protease (USP) performs critical functions beyond its enzymatic activity during virus replication.  Virology.  2013 March 15. 437(2):110-7.
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Jarosinski K.  Marek's disease virus late protein expression in feather follicle epithelial cells as early as 8 days postinfection.  Avian Dis.  2012 December. 56(4):725-31.
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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.
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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.
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Jarosinski K.  Dual infection and superinfection inhibition of epithelial skin cells by two alphaherpesviruses co-occur in the natural host.  PLoS One.  2012. 7(5):e37428.
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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.
[Link]

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.
[Link]

Jarosinski K, Hunt H, Osterrieder N.  Down-regulation of MHC class I by the Marek's disease virus (MDV) UL49.5 gene product mildly affects virulence in a haplotype-specific fashion.  Virology.  2010 September 30. 405(2):457-63.
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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.
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Jarosinski K, Osterrieder N.  Further analysis of Marek's disease virus horizontal transmission confirms that U(L)44 (gC) and U(L)13 protein kinase activity are essential, while U(S)2 is nonessential.  J Virol.  2010 August. 84(15):7911-6.
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Chbab N, Egerer A, Veiga I, Jarosinski K, Osterrieder N.  Viral control of vTR expression is critical for efficient formation and dissemination of lymphoma induced by Marek's disease virus (MDV).  Vet Res.  2010. 41(5):56.
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Buscaglia C, O'Connell P, Jarosinski K, Pevzner I, Schat K.  Selection for increased nitric oxide production does not increase resistance to Marek's disease in a primary broiler breeder line.  Avian Dis.  2009 September. 53(3):336-40.
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Fulton A, Peters S, Perkins G, Jarosinski K, Damiani A, Brosnahan M, Buckles E, Osterrieder N, Van de Walle G.  Effective treatment of respiratory alphaherpesvirus infection using RNA interference.  PLoS One.  2009. 4(1):e4118.
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Miller M, Jarosinski K, Schat K.  Negative modulation of the chicken infectious anemia virus promoter by COUP-TF1 and an E box-like element at the transcription start site binding deltaEF1.  J Gen Virol.  2008 December. 89(Pt 12):2998-3003.
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Van de Walle G, Jarosinski K, Osterrieder N.  Alphaherpesviruses and chemokines: pas de deux not yet brought to perfection.  J Virol.  2008 July. 82(13):6090-7.
[Link]

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.
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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.
[Link]

Jarosinski K, Schat K.  Multiple alternative splicing to exons II and III of viral interleukin-8 (vIL-8) in the Marek's disease virus genome: the importance of vIL-8 exon I.  Virus Genes.  2007 January. 34(1):9-22.
[Link]

Poonia B, Dunn P, Lu H, Jarosinski K, Schat K.  Isolation and molecular characterization of a new Muscovy duck parvovirus from Muscovy ducks in the USA.  Avian Pathol.  2006 December. 35(6):435-41.
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Jarosinski K, Tischer B, Trapp S, Osterrieder N.  Marek's disease virus: lytic replication, oncogenesis and control.  Expert Rev Vaccines.  2006 December. 5(6):761-72.
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Li X, Jarosinski K, Schat K.  Expression of Marek's disease virus phosphorylated polypeptide pp38 produces splice variants and enhances metabolic activity.  Vet Microbiol.  2006 October 31. 117(2-4):154-68.
[Link]

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.
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Miller M, Jarosinski K, Schat K.  Positive and negative regulation of chicken anemia virus transcription.  J Virol.  2005 March. 79(5):2859-68.
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Jarosinski K, Njaa B, O'connell P, Schat K.  Pro-inflammatory responses in chicken spleen and brain tissues after infection with very virulent plus Marek's disease virus.  Viral Immunol.  2005. 18(1):148-61.
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Yunis R, Jarosinski K, Schat K.  Association between rate of viral genome replication and virulence of Marek's disease herpesvirus strains.  Virology.  2004 October 10. 328(1):142-50.
[Link]

Jarosinski K, O'Connell P, Schat K.  Impact of deletions within the Bam HI-L fragment of attenuated Marek's disease virus on vIL-8 expression and the newly identified transcript of open reading frame LORF4.  Virus Genes.  2003 May. 26(3):255-69.
[Link]

Jarosinski K, Yunis R, O'Connell P, Markowski-Grimsrud C, Schat K.  Influence of genetic resistance of the chicken and virulence of Marek's disease virus (MDV) on nitric oxide responses after MDV infection.  Avian Dis.  2002 July. 46(3):636-49.
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Jarosinski K, Massa P.  Interferon regulatory factor-1 is required for interferon-gamma-induced MHC class I genes in astrocytes.  J Neuroimmunol.  2002 January. 122(1-2):74-84.
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Jarosinski K, Whitney L, Massa P.  Specific deficiency in nuclear factor-kappaB activation in neurons of the central nervous system.  Lab Invest.  2001 September. 81(9):1275-88.
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Jarosinski K, Jia W, Sekellick M, Marcus P, Schat K.  Cellular responses in chickens treated with IFN-alpha orally or inoculated with recombinant Marek's disease virus expressing IFN-alpha.  J Interferon Cytokine Res.  2001 May. 21(5):287-96.
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Massa P, Saha S, Wu C, Jarosinski K.  Expression and function of the protein tyrosine phosphatase SHP-1 in oligodendrocytes.  Glia.  2000 February 15. 29(4):376-85.
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Massa P, Whitney L, Wu C, Ropka S, Jarosinski K.  A mechanism for selective induction of 2'-5' oligoadenylate synthetase, anti-viral state, but not MHC class I genes by interferon-beta in neurons.  J Neurovirol.  1999 April. 5(2):161-71.
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Date Last Modified: 06/07/2014 - 21:56:23