Shresta Lab

Shresta Lab

"Infectious diseases have no geographic boundaries. It doesn’t matter whether a country is rich or poor, developed or developing, these diseases can still arrive." — Sujan Shresta, Ph.D. // Associate Professor
Center for Infectious Disease


Sujan Shresta, Ph.D., and her team study the immunology and virology of mosquito-borne human pathogens such as dengue virus (DENV) and Zika virus (ZIKV). DENV causes a spectrum of clinical disease ranging from dengue fever, a self-limited febrile illness, to a life-threatening syndrome called severe dengue or dengue hemorrhagic fever/dengue shock syndrome. ZIKV has been proven to cause serious birth defects, and is also associated with other neurological conditions including Guillain-Barré Syndrome and meningoencephalitis.

Studies suggest that the host’s immune system plays a dual role in protection and pathogenesis; however, how the immune response to DENV and ZIKV protects against or contributes to severe disease remains unclear and controversial. Using mouse models, primary human cell culture models, and patient samples, Dr. Shresta and her team dissect the protective versus pathogenic mechanisms of the immune system in response to these viral infections. As mosquito-borne viruses are increasingly spreading from tropical to temperate zones worldwide, the team has also begun to investigate the emergence of DENV and ZIKV in Nepal. A better understanding of the virus-host interactions is critical for developing much-needed antivirals and vaccines against DENV and ZIKV.

From The Lab

Jun 4, 2020

Fighting Mosquito-Borne Viruses Requires a Precise Balance of Immune Cells

Future vaccines will need to harness the power of T cells in preventing Zika fever and Japanese encephalitis
May 21, 2020 // Trends in Microbiology

What we can learn from SARS

Researchers comb through hundreds of studies to find clues to beating COVID-19
Nov 14, 2018 // Cell Host & Microbe

Maternally-acquired Zika immunity can increase dengue disease severity in mouse pups

The study is highly relevant for infants born in regions where both dengue and Zika virus are endemic
Nov 14, 2018 // NOVA PBS

How Zika and Dengue Exploit the Mother-Child Relationship

Due to the similarities between these closely-related viruses, mothers who have experienced Zika infections may have babies with a higher risk of suffering severe dengue, and vice versa.
Aug 2, 2018 // Nature Communications

Maternal dengue immunity protects against fetal damage in mice following Zika virus infection

Cytotoxic T-cells mobilized by dengue infection may combat catastrophic effects of Zika infection

Shresta Lab


J Med Chem

Targeting Endoplasmic Reticulum α-Glucosidase I With a Single-Dose Iminosugar Treatment Protects Against Lethal Influenza and Dengue Virus Infections

Warfield KL, Alonzi DS, Hill JC, Caputo AT, Roversi P, Kiappes JL, Sheets N, Duchars M, Dwek RA, Biggins J, Barnard…
Virol J

Investigation of the Immunogenicity of Zika Glycan Loop

Henderson EA, Tam CC, Cheng LW, Ngono AE, Nguyen AV, Shresta S, McGee M, Padgett H, Grill LK, Martchenko Shilman M
Curr Opin Immunol

Antigenic cross-reactivity between zika and dengue viruses: is it time to develop a universal vaccine?

Wen J, Shresta S
Sci Rep

Human polyclonal antibodies prevent lethal zika virus infection in mice

Branche E, Simon AY, Sheets N, Kim K, Barker D, Nguyen AT, Sahota H, Young MP, Salgado R, Mamidi A, Viramontes KM,…
Front Immunol

Cross-reactive T cell immunity to dengue and zika viruses: new insights Into vaccine development

Elong Ngono A, Shresta S

Zika virus protease cleavage of host protein septin-2 mediates mitotic defects in neural progenitors

Li H, Saucedo-Cuevas L, Yuan L, Ross D, Johansen A, Sands D, Stanley V, Guemez-Gamboa A, Gregor A, Evans T, Chen S, Tan…
Curr Opin Immunol

Antigenic cross-reactivity between zika and dengue viruses: is it time to develop a universal vaccine?

Wen J, Shresta S
PLoS Negl Trop Dis

Detection of zika virus in mouse mammary gland and breast milk

Regla-Nava JA, Viramontes KM, Vozdolska T, Huynh AT, Villani T, Gardner G, Johnson M, Ferro PJ, Shresta S, Kim K
Curr Opin Virol

Genome-wide approaches to unravelling host-virus interactions in dengue and zika infections

Carlin AF, Shresta S
PLoS Pathog

CD4+ T cells promote humoral immunity and viral control during zika virus infection

Elong Ngono A, Young MP, Bunz M, Xu Z, Hattakam S, Vizcarra E, Regla-Nava JA, Tang WW, Yamabhai M, Wen J, Shresta S
PLoS Negl Trop Dis

A longitudinal systems immunologic investigation of acute Zika virus infection in an individual infected while traveling to Caracas, Venezuela

Carlin AF, Wen J, Vizcarra EA, McCauley M, Chaillon A, Akrami K, Kim C, Ngono AE, Lara-Marquez ML, Smith DM, Glass CK,…
Cell Host Microbe

Maternally Acquired Zika Antibodies Enhance Dengue Disease Severity in Mice

Fowler AM, Tang WW, Young MP, Mamidi A, Viramontes KM, McCauley MD, Carlin AF, Schooley RT, Swanstrom J, Baric RS,…
Antiviral Res

Synergism between the tyrosine kinase inhibitor sunitinib and Anti-TNF antibody protects against lethal dengue infection

Branche E, Tang WW, Viramontes KM, Young MP, Sheets N, Joo Y, Nguyen AT, Shresta S
Proc Natl Acad Sci USA

Deconvolution of pro- and antiviral genomic responses in Zika virus-infected and bystander macrophages

Carlin AF, Vizcarra EA, Branche E, Viramontes KM, Suarez-Amaran L, Ley K, Heinz S, Benner C, Shresta S, Glass CK
Nat Commun

Cross-reactive Dengue virus-specific CD8+ T cells protect against Zika virus during pregnancy

Regla-Nava JA, Elong Ngono A, Viramontes KM, Huynh AT, Wang YT, Nguyen AT, Salgado R, Mamidi A, Kim K, Diamond MS,…
Annu Rev Immunol

Immune response to dengue and zika

Ngono AE, Shresta S
Sci Rep

Blocking zika virus vertical transmission

Mesci P, Macia A, Moore SM, Shiryaev SA, Pinto A, Huang CT, Tejwani L, Fernandes IR, Suarez NA, Kolar MJ, Montefusco S,…
Vaccines (Basel)

Development of zika virus vaccines

Makhluf H, Shresta S
Sci Rep

Repurposing of the anti-malaria drug chloroquine for zika virus treatment and prophylaxis

Shiryaev SA, Mesci P, Pinto A, Fernandes I, Sheets N, Shresta S, Farhy C, Huang CT, Strongin AY, Muotri AR, Terskikh AV
Nat Commun

Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent zika virus challenge

Wen J, Elong Ngono A, Regla-Nava JA, Kim K, Gorman MJ, Diamond MS, Shresta S
Cell Rep

An IRF-3-, IRF-5-, and IRF-7-independent pathway of dengue viral resistance utilizes IRF-1 to stimulate type I and II interferon responses

Carlin AF, Plummer EM, Vizcarra EA, Sheets N, Joo Y, Tang W, Day J, Greenbaum J, Glass CK, Diamond MS, Shresta S
J Interferon Cytokine Res

T cell immunity to zika and dengue viral infections

Wen J, Shresta S
Antiviral Res

Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists

Shiryaev SA, Farhy C, Pinto A, Huang CT, Simonetti N, Ngono AE, Dewing A, Shresta S, Pinkerton AB, Cieplak P, Strongin…
Cell Host Microbe

ADE-ing and abetting Zika

Wen J, Shresta S
Nat Microbiol

Identification of Zika virus epitopes reveals immunodominant and protective roles for dengue virus cross-reactive CD8+ T cells

Wen J, Tang WW, Sheets N, Ellison J, Sette A, Kim K, Shresta S

Modified mRNA vaccines protect against zika virus infection

Richner JM, Himansu S, Dowd KA, Butler SL, Salazar V, Fox JM, Julander JG, Tang WW, Shresta S, Pierson TC, Ciaramella…
Cell Host Microbe

Mapping and role of the CD8+ T cell response during primary zika virus infection in mice

Elong Ngono A, Vizcarra EA, Tang WW, Sheets N, Joo Y, Kim K, Gorman MJ, Diamond MS, Shresta S
Expert Opin Drug Discov

Novel strategies for discovering inhibitors of dengue and zika fever

Makhluf H, Kim K, Shresta S

Protective role of cross-reactive CD8 T cells against dengue virus infection

Elong Ngono A, Chen HW, Tang WW, Joo Y, King K, Weiskopf D, Sidney J, Sette A, Shresta S
Cell Stem Cell

Zika virus infects neural progenitors in the adult mouse brain and alters proliferation

Li H, Saucedo-Cuevas L, Regla-Nava JA, Chai G, Sheets N, Tang W, Terskikh AV, Shresta S, Gleeson JG
Trends Microbiol

Neuroterartogenic viruses and lessons for zika virus models

Kim K, Shresta S
Antiviral Res

Inhibition of endoplasmic reticulum glucosidases is required for in vitro and in vivo dengue antiviral activity by th eiminosugar UV-4

Warfield KL, Plummer EM, Sayce AC, Alonzi DS, Tang W, Tyrrell BE, Hill ML, Caputo AT, Killingbeck SS, Beatty PR, Harris…

Defining new therapeutics using a more immunocompetent mouse model of antibody-enhanced dengue virus infection

Pinto AK, Brien JD, Lam CY, Johnson S, Chiang C, Hiscott J, Sarathy VV, Barrett AD, Shresta S, Diamond MS
Current Opinion in Virology

Influence of antibodies and T cells on dengue disease outcome: insights from interferon receptor-deficient mouse models

Tang WW, Grewal R, Shresta S
Critical Reviews in Immunology

Innate antiviral immunity against dengue virus

Makhluf H, Shresta S
Journal of Immunology

Different STAT transcription complexes drive early and delayed responses to type I IFNs

Abdul-Sater AA, Majoros A, Plumlee CR, Perry S, Gu AD, Lee C, Shresta S, Decker T, Schindler C
Scientific Reports

Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy

Flingai S, Plummer EM, Patel A, Shresta S, Mendoza JM, Broderick KE, Sardesai NY, Muthumani K, Weiner DB
Journal of Virology

CD8+ T cells can mediate short-term protection against heterotypic dengue reinfection in mice

Zellweger RM, Tang WW, Eddy WE, King K, Sanchez MC, Shresta S
Journal of Virology

Dengue viral evolution under a hose-targeted antiviral

Plummer E, Buck MD, Sanchez M, Greenbaum JA, Turner J, Frewal R, Klose B, Sampath A, Warfield KL, Peters B, Ramstedt U,…

A novel iminosugar UV-12 with activity against the diverse viruses influenza and dengue (novel iminosugar antiviral for influenza and dengue)

Warfield KL, Plummer E, Alonzi DS, Wolfe GW, Sampath A, Nguyen T, Butters TD, Enterlein SG, Stavale EJ, Shresta S,…
Journal of Virology

Immunodominance changes as a function of the infecting dengue virus serotype and primary versus secondard infection

Weiskopf D, Angelo MA, Sidney J, Peters B, Shresta S, Sette A
Journal of Immunology

CD8+ T cells prevent antigen-induced antibody-dependent enhancement of dengue disease in mice

Zelleweger RM, Eddy WE, Tang WW, Miller R, Shresta S
Journal of Immunological Methods

Mouse models for dengue vaccines and antivirals

Plummer EM, Shresta S
Frontiers in Immunology

Mouse models to study dengue virus immunology and pathogenesis

Zellweger RM, Shresta S
Methods in Molecular Biology

Animal models in dengue

Plummer E, Shresta S
Advances in Virus Research

Dengue virus vaccine development

Yauch LE, Shresta S
Journal of Immunology

The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus

Chen HW, King K, Tu J, Sanchez M, Luster AD, Shresta S
PLoS Pathogens

Role of humoral versus cellular responses induced by a protective dengue vaccine candidate

Zellerger RM, Miller R, Eddy WE, White LJ, Johnston RE, Shresta S
Antiviral Research

Inhibitory and combinatorial effect of diphyllin, a v-ATPase blocker, on influenza viruses

Chen HW, Cheng JX, Liu MT, King K, Peng JY, Zhang XQ, Wang CH, Shresta S, Schooley RT, Liu YT
Proceedings of the National Academy of Sciences of the United States of America

Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells

Weiskopf D, Angelo MA, de Azeredo EL, Sidney J, Greenbaum JA, Fernando AN, Broadwater A, Kolla RA, De Silva AD, de…
Antiviral Research

An iminosugar with potent inhibition of dengue virus infection in vivio

Perry ST, Buck MD, Plummer EM, Penmasta RA, Batra H, Stavale EJ, Warfield KL, Dwek RA, Butters TD, Alonzi DS, Lada SM,…
PLoS One

Tracking the evolution of dengue virus strains D2S10 and D2S20 by 454 pyrosequencing

Makhluf H, Buck MD, King K, Perry ST, Henn MR, Shresta S
Journal of Virology

Gamma interferon (IFN-γ) receptor restricts systemic dengue virus replication and prevents paralysis in IFN-α/β receptor-deficient mice

Prestwood TR, Morar MM, Zellweger RM, Miller R, May MM, Yauche LE, Lada SM, Shresta S
Journal of Virology

Trafficking and replication patterns reveal splenic macrophages as major targets of dengue virus in mice

Prestwood TR, May MM, Plummer EM, Morar MM, Yauch LE, Shresta S

Role of complement in dengue virus infection: protection or pathogenesis?

Shresta S
Journal of Immunology

Insights into HLA-restricted T cell responses in a novel mouse model of dengue virus infection point toward new implications for vaccine design

Weiskopf D, Yauch LE, Angelo MA, John DV, Greenbaum JA, Sidney J, Kolla RV, De Silva AD, de Silva AM, Grey H, Peters B,…
Journal of Virology

Inhibition of dengue virus infections in cell cultures and in AG129 mice by a small interfering RNA targeting a high conserved sequence

Stein DA, Perty ST, Buck MD, Oehmen CS, Fischer MA, Poore E, Smith JL, Lancaster AM, Hirsch AJ, Slifka MK, Nelson JA,…
Expert Review of Anti-infective Therapy

Better late than never: antivirals for dengue

Perry ST, Buck MD, Shresta S
Antiviral Chemistry & Chemotherapy

Important advances in the field of anti-dengue virus research

Julander JG, Perry ST, Shresta S
PLoS Pathogens

STAT2 mediates innate immunity to Dengue virus in the absence of STAT1 via the type I interferon receptor

Perry ST, Buck MD, Lada SM, Schindler C, Shresta S
J Immunol

CD4+ T Cells Are Not Required for the Induction of Dengue Virus-Specific CD8+ T Cell or Antibody Responses but Contribute to Protection after Vaccination

Yauch LE, Prestwood TR, May MM, Morar MM, Zellweger RM, Peters B, Sette A, Shresta S
Cell Host Microbe

Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease

Zellweger RM, Prestwood TR, Shresta S

Principal Investigator

Sujan Shresta, Ph.D.

Associate Professor

Sujan Shresta joined LIAI in 2005 as an Assistant Professor and was promoted to Associate Professor in 2011. Dr. Shresta’s research focuses on the interface between immunology and virology, with particular interest in viral immunopathogenesis.

Dr. Shresta obtained her B.A. in Biological Sciences from Smith College and Ph.D. in Immunology from Washington University in St. Louis. She completed her post-doctoral training in Virology at the University of California, Berkeley. She received a Research Scholar Development award from the NIAID in 2005.

Lab Members

Robert Allen

Visiting Scientist

Emilie Branche

Postdoctoral Fellow

I obtained my Bachelor’s and Master’s of Science in Genetics and Cell Biology in 2007 and 2009, respectively, from Université Claude Bernard, Lyon, France. I completed my Ph.D. in Biology in October 2015 from Université de Genève, Switzerland after researching the effects of proteins that modulating lipid droplet biogenesis on hepatitis C virus life cycle. I joined Dr. Sujan Shresta’s laboratory in November 2016 as a postdoctoral fellow.

Research Focus:
My projects are focused on understanding virus-host interactions during infection of human macrophages and dendritic cells with dengue and Zika viruses using a systems immunology approach, and testing novel therapeutics against dengue and Zika using mouse models.

Career Goals:
I am very interested in developing treatments for emerging infectious diseases.

Andrew Gonzalez


Kenneth Kim

Visiting Scientist

Krishna Mandahar

Collaborating Scientist

Robyn Miller

Lab Manager

Kennis-Grace Mrotek

Intern (non-paid)

Jacqueline Ngo

Intern (non-paid)

Annie Elong Ngono, Ph.D.

Postdoctoral Fellow

I obtained my PhD from the University of Nantes (France) in Immunology, Molecular and Cellular Biology in 2013. I worked on the roles of myelin-specific T and B cells in multiple sclerosis. In January 2015, I began working as a postdoctoral fellow at LIAI studying virus-host cells interactions in animal models and human cells. My current projects focus on understanding the molecular mechanisms of the balance between protective and pathogenic T cell responses to flaviviruses, including Dengue and Zika.

Career Goals:
I am developing expertise in infectious diseases and plan to work in infectious disease public health, particularly to improve health systems in developing, low-income countries.

Donglim Park

Visiting Scientist

Nora Shafee

Postdoc Fellow (0 year)

Kristen Valentine

Postdoc Fellow (0 year)

Ying-Ting Wang

Visiting Scientist

Sara Yanke


Zhe Zhu

Visiting Scientist

Shresta Lab

Research Projects

Innate immune response to DENV and ZIKV

The IFN system is a major mechanism by which many viruses evade the cellular antiviral response. DENV and ZIKV can suppress Type I IFN signaling, but the exact mechanisms remain to be fully understood. Moreover, emerging literature indicates that the type I IFN system mediates antiviral immunity in a highly context-specific manner depending on the virus, cell type, and host species. Therefore, we have been using our mouse models to understand the mechanisms by which type I IFN contributes to antiviral immunity during DENV and ZIKV infection. We have previously determined that type I IFN production is regulated by two signaling pathways: the STAT1-dependent and the STAT1-independent pathways. We have defined the latter mechanism of protection against DENV infection to be the type I IFN receptor-STAT2 pathway, and revealed that the type I IFN receptor-STAT2 pathway, in the absence of STAT1, modulates type I IFN production and interferon-stimulated gene (ISG) response in a delayed manner. Studies are underway to define the particular interferon regulatory factor and ISG mechanisms through which both the STAT1-dependent and STAT2-independent pathways contribute to protection vs. pathogenesis using both mouse models and human cell culture models.

Adaptive immune response to DENV and ZIKV

Vaccine development for DENV is challenging in that the vaccine must induce long-lasting immunity against all four DENV serotypes (DENV1-4), as pre-existing immunity against a heterologous serotype may contribute to severe dengue disease (DHF/DSS). In particular, DENV-specific antibody responses may mediate antibody-dependent enhancement (ADE) of DENV infection under certain conditions. In 2010, we formally demonstrated ADE by developing a mouse mode of ADE-mediated disease, and we began to dissect the contribution of humoral vs. cellular immune components in dengue vaccine-mediated protection using model vaccine candidates as tools to probe the mechanisms by which the vaccine-induced immune responses in mice contribute to protection vs. ADE. Our studies have revealed a critical role for CD8 T-cell responses in dengue vaccine-mediated protection, and showed that the vaccine-induced antibody response can mediate ADE. Thus, contrary to the dogma that emphasizes the importance of humoral immunity alone, our findings imply that a DENV vaccine should induce both humoral and cellular responses to maximize efficacy and safety. In support of this assertion, our recent studies exploring the role of T cells in DENV reinfection and ADE settings have revealed that CD8 T-cells can actually abrogate ADE, suggesting a DENV vaccine that does not elicit CD8 T-cell responses may be dangerous. Since DENV and ZIKV are closely related and cross-reactive in many immunologic assays, it is currently uknown whether a first infection with one virus might protect or worsen a subsequent infection with the other virus. We are currently investigating the role of various T-cell costimulatory pathways in regulating the humoral and cellular responses to and between DENV and ZIKV, and are defining the particular pathways that should be targeted to maximize safety and efficacy of vaccines.

Development of vaccines against DENV and ZIKV

Emergence of mosquito-borne viruses such as DENV and ZIKV in Nepal