Alison Kell, PhD

Education

Dr. Kell completed her Bachelor’s degree in Ecology and Evolutionary Biology at the University of Colorado in 2005. She received a PhD at the University of Washington with Dr. Gael Kurath, developing novel in vivo superinfection assays to determine phenotypic and genetic correlates of viral fitness for the salmonid rhabdovirus, Infectious Hematopoietic Necrosis virus.

To fully appreciate the impact of host immune pressure on viral fitness, evolution, and pathogenesis, she joined the laboratory of Dr. Michael Gale, Jr at the University of Washington as a postdoctoral fellow in 2013. Dr. Kell brings her research program to the Department of Molecular Genetics and Microbiology in January 2020.

Key Publications

J Schwerk, F Soveg, A Ryan, K Thomas, L Aarreberg, S Ozarkar , A Forero, AM Kell, J Roby, L So, M Gale Jr., M Daugherty, R Savan. Zinc-finger antiviral protein isoforms orchestrate virus restriction and interferon resolution activities. Nature Immunology. 2019.

A Jarret, AP McFarland, SM Horner, AM Kell, J Schwerk, M Hong, S Badil, RC Joslyn, DP Baker, M Carrington, CH Hagedorn, M Gale Jr, R Savan. Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling. Nature Medicine. 2016 Nov 14. PMID: 27841874

M Hong, J Schwerk, C Lim, AM Kell, A Jarret, J Pangallo, YM Loo, S Liu, CH Hagedorn, M Gale Jr, R Savan. Interferon lambda 4 expression is suppressed by the host during viral infection.  Journal of Experimental Medicine. 2016 Oct 31. PMID: 27799623 

J Xu, X Mercado-López, JT Grier, W Kim, LF Chuna, EB Irvine, Y Del Toro Duany, AM Kell, S Hur, M Gale Jr., A Raj, CB López. Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I. MBio 2015. 6;6(5):e01265-15. PMID: 26443454. 

AM Kell, M Stoddard, H Li, J Marcotrigiano, GM Shaw, M Gale, Jr. PAMP Recognition of Hepatitis C Virus Transmitted/founder Variants by RIG-I is dependent on U-Core length. Journal of Virology. 2015. PMID: 26311867.

AM Kell, M Gale Jr. RIG-I in RNA virus recognition. Virology. 2015 May;479-480:110-21.

AM Kell, AR Wargo, G Kurath. Viral fitness does not correlate with three genotype displacement events involving infectious hematopoietic necrosis virus. Virology. 2014 Sep;464-465:146-55.

AM Kell, AR Wargo, G Kurath. The role of virulence for in vivo superinfection fitness of a vertebrate RNA virus. Journal of Virology. 2013 Jul;87(14):8145-57.

A Schiavi, A Torgovnick, AM Kell, E Megalou, N Castelein, I Guccini, L Marzocchella, S Gelino, M Hansen, F Malisan, I Condo’, R Bei, S Rea, B. P. Braeckman, N Tavernarakis, R Testi, N Ventura. Autophagy induction extends lifespan and reduces lipids content in response to frataxin silencing in C. elegans. Experimental Gerontology. 2012. Dec 13. pii: S0531-5565(12)00315-4.

AR Wargo, AM Kell, RJ Scott, GH Thorgaard, G Kurath. Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load. Virus Research. 2012. Apr;165(1):71-80.

NW Kahn, SL Rea, S Moyle, AM Kell, TE Johnson. Proteosomal dysfunction activates the transcription factor SKN-1 and produces a selective oxidative stress response in Caenorhabditis elegans. The Biochemical Journal. 2008. 409(1);205-13.

AM Kell, N Ventura, N Kahn, and TE Johnson. Activation of SKN-1 by Novel Kinases in Caenorhabditis elegans. Free Radical Biology & Medicine. 2007. 43(11);1560-6.

Research

The Kell lab is focused on defining the virus-host interactions in pathogenic Old World hantavirus infection, and their molecular mechanisms, that program innate immunity and differential disease outcome among reservoir rodent hosts and humans. Hantaviruses are zoonotic RNA viruses found in insectivore and rodent hosts worldwide, establishing asymptomatic, persistent infections in their respective reservoir hosts.

In contrast, hantaviruses can cause severe disease in humans, hantavirus cardiopulmonary syndrome (HPS) or hantavirus fever and renal syndrome (HFRS). We utilize comparative immunology and genomics approaches to identify and interrogate differences in host innate immune responses and viral antagonism that correspond to divergent disease outcomes in hantavirus infections of reservoir and non-reservoir hosts.

The Kell lab is recruiting! Interested research scientists, graduate students, and postdoctoral fellows should email a cover letter and CV to Dr. Kell at: AMKell@salud.unm.edu

Pathogen Recognition & Innate Immune Antagonism

The innate immune response is the first line of defense against viral infection. Our studies suggest that the cytosolic pathogen recognition receptors, RIG-I and MDA5, are required for early innate immune activation following Hantaan virus (HTNV) infection of human endothelial cell cultures, which are known targets of infection.

However, these pathogen recognition receptors are not required for viral clearance in non-reservoir rodents in vivo. The lab has active projects to investigate the signaling pathways in human target endothelial cells that are activated in response to HTNV infection and defining the mechanisms of innate immune antagonism by HTNV in vitro and in vivo.

Mechanisms Underlying Infection Outcome

Using a comparative genomics approach, we interrogated reservoir rodent (rat) and non-reservoir (human) endothelial cells infected with the Seoul orthohantavirus (SEOV) by RNA-sequencing to identify host-specific responses to hantavirus infection.

Bioinformatics analysis suggests differential modulation of endothelial activation and the vascular endothelial growth factor (VEGF) receptor signaling pathway when comparing reservoir and non-reservoir transcriptional responses following infection. The lab is interested in defining these host-specific differences in functional responses in endothelial cells and the virus-host interactions that drive these responses following SEOV infection.