Asit K. Pattnaik, Ph.D.

Professor
University of Nebraska-Lincoln
School of Veterinary and Biomedical Sciences
109 Morrison Center
Lincoln, NE 68583-0900

Telephone: (402) 472-1067
Fax: (402) 472-3323
E-mail: apattnaik2@unl.edu

Research Program

Studies in my laboratory focus on molecular biology of replication and immunopathogenesis of human and animal RNA viruses. Over the years, we have been studying vesicular stomatitis virus (VSV), a non-segmented negative-strand RNA virus in the family Rhabdoviridae in the order Mononegavirales to understand the mechanisms of viral RNA transcription, replication as well as virus assembly. VSV has served as an excellent paradigm for many negative-strand RNA viruses to understand the basic mechanisms of the genetic expression of this group of viruses, which include some of the most important human pathogens such as rabies virus, respiratory syncytial virus, Ebola virus, measles virus, etc. Our laboratory also researches on porcine reproductive and respiratory syndrome virus (PRRSV), a positive-strand RNA virus in the family Arteriviridae and order Nidovirales. PRRSV is an economically important pathogen, causing serious diseases in swine worldwide. In addition, we have been studying the recently emerged Zika virus (ZIKV) to understand the immunopathogenic mechanisms of the virus and develop vaccines and antivirals. Currently, our lab has initiated studies on the emerging SARS-CoV-2 in attempts to generate vaccines by multiple different approaches. Overall, our research focus on the understanding of the mechanism(s) of gene expression and its regulation as well as pathogenesis are essential for identifying virus-specific targets for therapeutic intervention in controlling infection by these viruses.

Using VSV, we had previously developed a completely cDNA-based reverse genetic system (Cell, 69:1011-1020, 1992), which has allowed us to introduce specific genetic alterations into the genome of VSV and its defective interfering particles and examine the effects of these alterations on transcription and replication of the viral genomes. The system laid the foundation for genetic manipulation of all negative-strand RNA viruses and has been used extensively by investigators worldwide to generate infectious molecular clones of the negative-strand RNA viruses. Using the system, previous studies from our laboratory addressed three major areas of research: (1) understand the role of nucleotide sequences within the viral genome that control transcription and replication processes; (2) understand structure-function relationships of the viral proteins involved in genome replication, transcription, and virus assembly; and (3) generate and characterize recombinant VSV encoding heterologous viral proteins for vaccine development. We are currently examining the role of host cell functions in viral genome replication by employing genome-wide siRNA screens. A human genome-wide siRNA screening study (Proc. Natl. Acad. Sci., USA, 108(47): 19036-19041, 2011) identified many important cellular pathways and host cell factors required for infection and replication of VSV.  Current studies are directed at understanding of the mechanisms of the involvement of these cellular proteins and pathways in VSV gene expression.

For studies related to PRRSV replication and immune response in infected pigs and cultured cells, we constructed a full-lenght cDNA clone of the entire viral genome from which infectious virus could be readily recovered (Virology, 325:308-319, 2004). Using this infectious cDNA clone, we have addressed many questions regarding replication and pathogenesis of this important swine pathogen. We have shown that the PRRSV evades host cells’ immune response by employing “glycan shielding” mechanism (JVI, 80:3994-4004, 2006; JVI, 85:5555-5564, 2011), which will have significant impact on PRRSV vaccine development. By generating an infectious clone of a vaccine strain of PRRSV (Vaccine, 24:7071-80, 2006), we have mapped the determinants of virulence and attenuation of PRRSV (Virology, 380:371-378, 2008). Our studies have identified the viral glycoproteins that interact with the receptor for entry of the virus into the host cells (JVI, 84:1731-1740, 2010; Virology, 410:385-394, 2011). We have also shown that several of the PRRSV nonstructural proteins possess the inherent ability to suppress the host cell’s innate immune response (JVI, 84:1574-1584, 2010; Virology, 406: 270-279, 2010; JVI, 85, 12939-12949., 2011). These studies along with other ongoing studies in our laboratory position us to generate second generation differential PRRSV vaccines by reverse genetic methods.

With the emergence of ZIKV epidemic and most recent SARS-CoV-2COVID-19 pandemic, we have been studying immunopathogenic mechanisms of these viruses. We have generated the infectious molecular clone of ZIKV and have shown that glycosylation of its envelope (E) protein and NS1 proteins are important determinants of viral neuroinvasioin and virulence (JVI, 91(23): e01348-17, 2017; Vaccines (Basel), 7(3):112, 2019). Viruses encoding unglycosylated E and NS1 proteins are significantly attenuated in mice model and are being further investigated as potential vaccine candidates. In addition, we have also identified small molecule inhibitors of ZIKV through in silico analysis by targeting the viral polymerase (Antiviral Res, 151: 78-86, 2018). Current attempts are focused on developing vaccine candidates for ZIKV and SARS-CoV-2 using several different approaches.

Selected Recent Publications

Pattnaik, A. Sahoo, B. R. and Pattnaik, A. K. (2020). Current Status of Zika Virus Vaccines: Successes and Challenges. Vaccines (Basel), In Press.

Gallardo-Vara, E., Ruiz-Llorente, L., Casado-Vela, J., Ruiz-Rodríguez, M. J., López-Andrés, N., Pattnaik, A. K., Quintanilla, M. and Bernabeu, C. (2019). Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners.  Cells, 8(9): 1082. PMID: 31540324

Annamalai, A. S., Pattnaik, A., Sahoo, B. R., Guinn, Z. P., Bullard, B. L., Weaver, E. A., Steffen, D., Natarajan, S. K., Petro, T. M., Pattnaik, A. K. (2019). An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model. Vaccines (Basel), 7(3): 112. PMID: 31547297

Pattnaik, A., Palermo, N., Sahoo, B. R., Yuan, Z., Hu, D., Annamalai, A. S., Vu, H. L. X., Correas, I., Prathipati, P. K., Destache, C. J., Li, Q., Osorio, F. A., Pattnaik, A. K., Xiang, S. H. (2018). Discovery of a non-nucleoside RNA polymerase inhibitor for blocking Zika virus replication through in silico screening. Antiviral Res, 151: 78-86. PMID: 29274845

Annamalai, A. S., Pattnaik, A., Sahoo, B. R., Muthukrishnan, E., Natarajan, S. K., Steffen, D., Vu, H. L. X., Delhon, G., Osorio, F. A., Petro, T. M., Xiang, S. H., Pattnaik, A. K. (2017). Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated and Defective in Neuroinvasion. J. Virology, 14;91(23): e01348-17. PMID: 28931684

Vu, H. L. X., Pattnaik, A. K., and Osorio, F. A. (2017). Strategies to broaden the cross-protective efficacy of vaccines against porcine reproductive and respiratory syndrome virus. Vet. Microbiol, 206: 29-34 PMID: 27692670

Kimpston-Burkgren, K., Correas, I., Osorio, F. A., Steffen, D., Pattnaik, A. K., Fang, Y., Vu, H. L. X. (2017). Relative contribution of porcine reproductive and respiratory syndrome virus open reading frames 2-4 to the induction of protective immunity. Vaccine, 35(34): 4408-4413. PMID: 28689650

Correas, I., Osorio, F. A., Steffen, D., Pattnaik, A. K., Vu, H. L. X. (2017). Cross reactivity of immune responses to porcine reproductive and respiratory syndrome virus infection. Vaccine, 35(5): 782-788. PMID: 28062126

Sun, H., Pattnaik, A. K., Osorio, F. A., Vu, H. L. X. (2016). Identification of viral genes associated with the interferon-inducing phenotype of a synthetic porcine reproductive and respiratory syndrome virus strain. Virology, 499: 313-321. PMID: 27736706

Das, A., Dinh, P. X., Pattnaik, A. K. (2015). Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral response. Virology, 485: 383-92. PMID: 26342464

Massilamany, C., Gangaplara, A., Basavalingappa, R. H., Rajasekaran, R. A., Vu, H., Riethoven, J. J., Steffen, D., Pattnaik, A. K., Reddy, J. (2015). Mutations in the 5' NTR and the Non-Structural Protein 3A of the Coxsackievirus B3 Selectively Attenuate Myocarditogenicity. PLoS One, 10(6): e0131052. PMID: 26098885

Das, A., Dinh, P. X., Panda, D., Pattnaik, A. K. (2014). Interferon-inducible protein IFI35 negatively regulates RIG-I antiviral signaling and supports vesicular stomatitis virus replication. J. Virology, 88(6): 3103-13. PMID: 24371060

Dinh, P. X., Beura, L. K., Das, P. B., Panda, D., Das, A., and Pattnaik, A. K. (2013). Induction of Stress Granule (SG)-Like Structures in Vesicular Stomatitis Virus-Infected Cells. J. Virology, 87(1):372-383. PMID: 23077311

Hasan, M., Koch, J., Rakheja, D., Pattnaik, A. K., Brugarolas, J., Dozmorov, I., Levine, B., Wakeland, E. W., Lee-Kirsch, M. A., and Yan, N. (2013). Trex1 regulates lysosomal biogenesis and interferon-independent activation of antiviral genes. Nature Immunology, 14(1):61-71. PMID: 23160154

Pattnaik, A. K. and Dinh, P. X. (2013). Manipulation of Cellular Processing Bodies (PBs) and Their Constituents by Viruses. DNA and Cell Biology, 32(6): 286-291. PMID: 23617258

Dinh, P. X., Das, A., Franco, R., and Pattnaik, A. K. (2013). hnRNP K Supports Vesicular Stomatitis Virus Replication by Regulating Cell Survival and Cellular Gene Expression. J Virology,  87(18):10059-10069. PMID: 23843646

Vu, H. L., Kwon, B., de Lima, M., Pattnaik, A. K. and Osorio, F. A. (2013). Characterization of a serologic marker candidate for development of a live-attenuated DIVA vaccine against porcine reproductive and respiratory syndrome virus, Vaccine, 31:4330-4337.  PMID: 23892102

Beura, L. K., Subramaniam, S., Kwon, B. J., Vu, H. L. X., Pattnaik, A. K., and Osorio, F. A. (2012). Identification of amino acid residues important for anti-IFN activity of porcine reproductive and respiratory syndrome virus non-structural protein 1. Virology, 433(2):431-9. PMID: 22995188

Dinh, P. X., Panda, D., Das, P. B., Das, S. C., Das, A., and Pattnaik, A. K. (2012). A single amino acid change resulting in loss of fluorescence of eGFP in a viral fusion protein confers fitness and growth advantage to the recombinant vesicular stomatitis virus. Virology, 432(2): 460-469.  PMID: 22832124

Subramaniam, S., Beura, L. K., Kwon, B. J., Pattnaik, A. K., and Osorio, F. A. (2012). Amino Acid Residues in the Non-Structural Protein 1 of Porcine Reproductive and Respiratory Syndrome Virus Involved in Down-Regulation of TNFa expression In Vitro and Attenuation In Vivo. Virology, 432(2): 241-249. PMID: 22699004

Gangaplara, A., Massilamany, C., Brown, D. M., Delhon, G., Pattnaik, A. K., Chapman, N., Rose, N., Steffen, D., and Reddy, N. J. (2012). Coxsackievirus B3 infection leads to the generation of cardiac myosin heavy chain-α-reactive CD4 T cells in A/J mice. Clinical Immunology, 144(3): 237-249. PMID: 22854287

Marozin, S., Altomonte, J., Apfel, S., Dinh, P. X., De Toni, E., Rizzani, A., Nussler, A., Kato, N., Schmid, R., Pattnaik, A. K., and Ebert, O. (2012). Post-Translational Modification of VSV G Protein, but not JNK inhibition, is the antiviral mechanism of SP600125. J. Virology, 86(9): 4844-4855. PMID: 22345438

Du, Y., Pattnaik, A. K., Song, C., Yoo, D. and Li, G. (2012). Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts. Virology, 424(1):18-32. PMID: 22222209

Panda, D., Das, A., Dinh, P. X., Subramaniam, S., Nayak, D., Barrows, N. J., Pearson, J. L., Thompson, J., Kelly, D. L., Ladunga, I., and Pattnaik, A. K. (2011). RNAi Screening Reveals Requirement for Host Cell Secretory Pathway in Infection by Diverse Families of Negative-Strand RNA Viruses. Proc. Natl. Acad. Sci., USA, 108(47): 19036-19041. PMID: 22065774

Beura, L. K., Dinh, P. X., Osorio, F. A., and Pattnaik, A. K. (2011). Cellular Ploy(C) Binding Proteins 1 and 2 Interact with Porcine Reproductive and Respiratory Syndrome Virus Non-Structural Protein 1β and Support Viral Replication. J. Virology, 85(24): 12939-12949. PMID: 21976648

Dinh, P. X., Beura, L. K., Panda, D., Das, A., and Pattnaik, A. K. (2011). Antagonistic Effects of Cellular Poly(C) Binding Proteins on Vesicular Stomatitis Virus Gene Expression. J. Virology, 85(18): 9459-9471. PMID: 21752917

Vu, H. L. X., Kwon, B. J., Yoon, K.-J, Laegreid, W. W., Pattnaik, A. K., and Osorio, F. A. (2011). Immune Evasion of porcine reproductive and respiratory syndrome virus through glycan shielding involved glycoprotein 5 as well as glycoprotein3. J. Virology, 85(11): 5555-5564. PMID: 21411530

Panda, D. and Pattnaik, A. K. (2011). Transcription of Vesicular Stomatitis Virus RNA Genome. In: Negative Strand RNA Virus (Edited by: Luo, M.), Chapter 8, pp. 149-173. World Scientific Publishing Co. Pte. Ltd., Hackensack, NJ, USA.

Das, P.B., Vu, H.L., Dinh, P.X., Cooney, J.L., Kwon, B., Osorio, F.A., Pattnaik, A.K. (2011). Glycosylation of minor envelope glycoproteins of PRRSV in infectious virus recovery, receptor interaction, and immune response. Virology, 410(2):385-394. PMID: 21195444

Subramaniam, S., Kwon, B. J., Beura, L. K., Kuszynski C. A., Pattnaik, A. K., and Osorio, F. A. (2010). Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-kB and Sp1. Virology, 406(2): 270-279. PMID: 20701940

Panda, D., Dinh, P. X., Beura, L. K., and Pattnaik, A. K. (2010). Induction of Interferon and Interferon Signaling Pathways by Replication of Defective Interfering Particle RNA in Cells Constitutively Expressing Vesicular Stomatitis Virus Replication Proteins. J. Virology, 84(9):4826-4831. PMID: 20181705

Das, P. B., Dinh, P. X., Ansari, I. H., de Lima, M., Osorio, F. A., and Pattnaik, A. K. (2010). The Minor Envelope Glycoproteins GP2a and GP4 of Porcine Reproductive and Respiratory Syndrome Virus Interact with the Receptor, CD163. J. Virology, 84(4): 1731-1740. PMID: 19939927

Beura, L. K., Sarkar, S. N., Kwon, B. J., Subramaniam, S., Jones, C., Pattnaik, A. K., and Osorio, F. A. (2010). Porcine Reproductive and Respiratory Syndrome Virus nonstructural protein nsp1β modulates host immune response by antagonizing IRF3 activation. J. Virology, 84(3): 1574-1584. PMID: 19923190

Pattnaik, A. K. and Panda, D. (2009). Biarsenical Labeling of Tetracysteine-Tagged Proteins for Tracking Existing and Newly Synthesized Pools of Proteins. CSH Protocols; doi:10.1101/ pdb.prot5343 PMID: 20150090

de Lima, M.  Ansari, I. H., Das, P. B., Ku, B., Martinez-Lobo, F. J., Pattnaik, A. K., and Osorio, F. A. (2009). GP3 is a Structural Component of the PRRSV Type II Virion. Virology, 390(1):31-36. PMID: 19467555

Nayak, D., Panda, D., Das, S. C., Luo, M., and Pattnaik, A. K. (2009). Single Amino Acid Alterations in a Highly Conserved Central Region of Vesicular Stomatitis Virus N Protein Differentially Affect the Viral Nucleocapsid Template Functions. J. Virology, 83(11):5525-5534. PMID: 19321605

Das, S. C., Panda, D., Nayak, D., and Pattnaik, A. K. (2009). Biarsenical Labeling of Vesicular Stomatitis Virus Encoding Tetracysteine-Tagged M Protein Allows Dynamic Imaging of M Protein and Virus Uncoating in Infected Cells. J. Virology, 83(6):2611-2622. PMID: 19153240

de Lima, M., Kwon, B., Ansari, I. H., Pattnaik, A. K., Flores, E. F., and Osorio, F. A. (2008). Development of a porcine reproductive and respiratory syndrome virus differentiable (DIVA) strain through deletion of specific immunodominant epitopes. Vaccine, 26(29-30):3594-3600. PMID: 18538899

You, J. H., Howella, G., Pattnaik, A. K., Osorio, F. A., and Hiscox, J. A.  (2008). A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus nucleocapsid protein based on live cell imaging. Virology, 378(1):34-47. PMID: 18550142

Kwon, B. J., Ansari, I. H., Pattnaik, A. K., and Osorio, F. A. (2008). Identification of virulence determinants of Porcine Reproductive and Respiratory Syndrome virus through construction of chimeric clones. Virology, 380(2):371-378. PMID: 18768197

Luyet, P. P. T. Falguieres, V. Pons, A. K. Pattnaik, and J. Gruenberg. (2008). The ESCRT-I Subunit TSG101 Controls Endosome-to-Cytosol Release of Viral RNA. Traffic, 9(12):2279-2290. PMID: 18817529

Otsuka, M., Jing, Q., Georgel, P., New, L., Chen, J., Mols, J., Kang Y. J., Jiang, Z., Du X, Cook R, Das, S. C., Pattnaik, A. K., Beutler, B., and Han, J. (2007). Hypersusceptibility to vesicular stomatitis virus infection in dicer-deficient mice is due to impaired miR24 and miR93 expression. Immunity, 27(1):123-134. PMID: 17613256

Kwon, B. J., Ansari, I. H., Osorio, F. A., and Pattnaik, A. K. (2006). Infectious clone-derived viruses from virulent and vaccine strains of porcine reproductive and respiratory syndrome virus mimic biological properties of their parental viruses in a pregnant sow model. Vaccine, 24(49-50):7071-80. PMID: 17049689

de Lima, M., Pattnaik, A. K., Flores, E. F., and Osorio, F. A. (2006). Serologic marker candidates identified amongst B-cell linear epitopes of Nsp2 and structural proteins of a North American strain of Porcine Reproductive and Respiratory Syndrome virus. Virology, 353(2):410-421. PMID: 16843516

Das, S. C., Nayak, D., Zhou, Y., and Pattnaik, A. K. (2006). Visualization of Intracellular Transport of Vesicular Stomatitis Virus Nucleocapsids in Living Cells. J. Virology, 80(13):6368-6377. PMID: 16775325

Ansari, I. H., Kwon, B. J., Osorio, F. A., and Pattnaik A. K. (2006). Influence of N-Linked Glycosylation of Porcine Reproductive and Respiratory Syndrome Virus GP5 on Virus Infectivity, Antigenicity, and Ability to Induce Neutralizing Antibodies. J. Virology, 80(8):3994-4004. PMID: 16571816

 

More publications can be found at PubMed

EDUCATION

M.S. in Life Sciences, 1978
Jawaharlal Nehru University, New Delhi, India.

Ph.D. Molecular Virology, 1984
Griffith University, Brisbane, Australia.

PROFESSIONAL POSITIONS

2005-Present: Professor, Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, NE.

11/2002-2005: Associate Professor, Department of Veterinary and Biomedical Sciences,
University of Nebraska-Lincoln, NE.

1999-2002: Associate Professor, Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL.

10/1992-5/1999: Assistant Professor, Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL.

1987-1992: Research Associate, Department of Microbiology, University of Alabama at Birmingham Medical School, Birmingham, AL

1984-1987: Post-doctoral Fellow, Department of Microbiology and Immunology, UCLA School of Medicine, University of California at Los Angeles, CA.

HONORS AND PROFESSIONAL AFFILIATIONS

Council of Scientific and Industrial Research (CSIR, India) Fellowship, 1978-1980, Jawaharlal Nehru University, New Delhi, India

Postgraduate Research Scholarship, 1980-1983, Griffith University, Brisbane, Australia

The Stanley Glaser Research Foundation Award, University of Miami, 1993

Honored for Outstanding Contribution in the Field of Molecular Virology, Recipient of J. B. Haldane Memorial Award, KIIT University, INDIA, 2013

Guest Lecturer for a minicourse on “Vaccines Against Human Viral Pathogens”, Sponsored by the Government of India through the Global Initiative in Academic Network (GIAN) Program, Indian Institute of Technology, Indore, India, July 2018.

Member, ASM (1987-present); ASV (1989-present); AAAS (1994-present); Society for General Microbiology, U.K. (1994-2014).