About

Gary Whittaker, PhD, is the James Law Professor of Virology and the Director of Graduate Studies in the Graduate Field of Public Health and Planetary Health at Cornell University College of Veterinary Medicine. He is a member of the Departments of Microbiology & Immunology and Public & Ecosystem Health. Dr. Whittaker's research focuses on the structure and function of viral envelope proteins, specifically how genomic mutations lead to changes in these proteins and influence viral pathogenesis in influenza viruses and coronaviruses, including SARS-CoV, MERS-CoV, and feline coronaviruses. His work also involves the development of novel vaccines and diagnostic tests. He earned his PhD from the University of Leeds in the UK in 1991, with a focus on herpesvirus glycoproteins, and conducted post-doctoral studies on influenza virus at Yale Medical School before joining Cornell in 1996. Dr. Whittaker has received recognition for his research, including the Pfizer/Zoetis Animal Health Award for Research Excellence in 2001, and is actively involved in professional organizations such as the International Society for Companion Animal Diseases and the Cornell K. Lisa Yang Center for Wildlife Health.

Research topics

• Biology
• Virology
• Medicine
• Biochemistry
• Computational biology
• Genetics
• Zoology
• Evolutionary biology
• Chemistry
• Cell biology

Selected publications

• Identification of within-host deletions in domain 0 of the spike gene of highly pathogenic feline coronavirus type 2 from the United States

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-15

  preprintOpen accessSenior authorCorresponding

  Abstract Feline coronavirus (FCoV) is known to gain pathogenicity within-host to cause the lethal disease feline infectious peritonitis (FIP). Most FIP cases are caused by viruses in genotype 1 (FCoV-1) via an ‘internal mutation’ in the spike gene. However, genotype 2 (FCoV-2) has risen to prominence based on the emergence of FCoV-23, a highly pathogenic novel variant from Cyprus that has a deletion in the N-terminus (domain 0) of spike. Here, we conducted a retrospective molecular study of FCoV-2 detected in three cats in the U.S. during 2013 and 2016. Whole-genome sequencing revealed that the two cats exhibiting long-term signs each had an FCoV-2 with a distinct deletion in domain 0 of spike in all examined tissues. The epidemiologically-linked cat displaying signs for a short duration had an FCoV-2 with an intact spike. Our results suggest that this “internal deletion” in the spike gene is a biomarker of highly pathogenic FCoV-2. Graphical abstract

  PublisherOA PDFDOI

• Broad-spectrum synthetic carbohydrate receptors (SCRs) inhibit viral entry across multiple virus families

  Science Advances · 2025-08-27 · 5 citations

  articleOpen access

  Viral pandemics continue to threaten global health and economic stability. Despite medical advances, the absence of broad-spectrum antivirals (BSAs) prevents rapid responses to emerging viral threats. This is largely due to the lack of universal drug targets across diverse viral families and high variability among viral proteins. In this study, we evaluated 57 synthetic carbohydrate receptors (SCRs) for antiviral activity in cellulo using pseudotyped virus particles (PVPs) from six high-risk viruses across three families: Paramyxoviridae, Filoviridae, and Coronaviridae. Four SCRs inhibited all tested PVPs, and their efficacy was confirmed against live viruses including SARS-CoV-2, MERS-CoV, EBOV, MARV, NiV, and HeV. Notably, SCR005 and SCR007 , which exhibited minimal toxicity, significantly reduced SARS-CoV-2 infection in a severe animal model with a single dose. Mechanistic studies suggested that SCRs bind viral envelope N-glycans, blocking viral attachment and/or fusion. These results identify conserved viral N-glycans as promising BSA targets and establish SCRs as candidate prophylactic agents against enveloped viruses with pandemic potential.

  PublisherDOI

• Rapid Clinical Resolution and Differential Diagnosis of a Neurological Case of Feline Infectious Peritonitis (FIP) Using GS-441524

  Pathogens · 2025-04-27 · 1 citations

  articleOpen accessSenior authorCorresponding

  Case summary: A 2-year-old male neutered domestic shorthair cat was presented with a progressive history of tetraparesis, ataxia, and inappetence over 4 days. A physical exam revealed mucopurulent nasal discharge and stertor. A neurologic exam revealed a multifocal neurolocalization. The cat was non-ambulatory tetraparetic and developed seizures while in hospital. Hematologic assessment revealed anemia, hypoalbuminemia and hyperglobulinemia. Magnetic resonance imaging (MRI) of the brain revealed multifocal meningeal contrast enhancement in the brainstem and cervical spine, as well as mandibular and retropharyngeal lymphadenopathy. Cerebrospinal fluid revealed marked neutrophilic pleocytosis; no infectious organisms were seen. Toxoplasma IgG/IgM and Cryptococcus antigen latex agglutination were negative. Mandibular and abdominal lymph nodes were aspirated, and cytology revealed mixed inflammation. The cat was suspected to have feline infectious peritonitis, and to aid in clinical diagnosis he was enrolled in research study—with targeted Nanopore-based sequencing specifically identifying and characterizing FCoV-1 RNA in spinal fluid and anal swab, but not in urine. The cat was treated with anticonvulsants (phenobarbital and levetiracetam), an antibiotic (ampicillin/clavulanic acid), and GS-441524. Neurologic signs did not improve on an antibiotic alone but improved significantly after two subcutaneous injections of GS-441524. The cat received an 84-day course of GS-441524 and, at the time of manuscript preparation (over 12 months after diagnosis), remains ambulatory and seizure-free without recurrence of neurologic signs and no detectable viral shedding in feces.

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• Trash Talking: Anthropogenic Resources Facilitate Raccoon Interactions in Urban Environments

  Ecology and Evolution · 2025-12-01 · 2 citations

  articleOpen access

  Interactions between animals of the same species underpin many ecological processes, from reproduction to pathogen transmission. Habitat modification, such as urbanization, affects an animal's spatial behavior, altering interactions with both their habitat and conspecifics. Raccoon space use varies widely between urban/suburban and rural populations, with anthropogenic resources suggested as a key factor in shaping movement behavior and consequently, opportunities for conspecific interaction. Here, we use high-resolution GPS data to identify instances of close spatiotemporal proximity (i.e., co-occurrence), referred to as "contacts," among raccoons in an urban greenspace in Brooklyn, New York City (NYC). To understand how resource patterning affects contact formation processes and evaluate possible spatial and demographic factors contributing to the types of contact observed, we evaluated the effect of proximity to different resources (including anthropogenic subsidies) on the probability of urban raccoon contact and assessed associations between the characteristics of urban raccoon contact events. We found that certain resources increase the likelihood of urban raccoons coming into contact, with the largest positive effect observed for anthropogenic resources. Shared characteristics across contact events suggest three main types of co-occurrence: (1) longer duration contacts between males near anthropogenic resources, (2) proximity between females near fruiting plants or while denning, and (3) transient interactions between males and females. We conclude that in an urban habitat, anthropogenic subsidies are important drivers of co-occurrence between raccoons, which interact dynamically with social factors to shape the characteristics, frequency, and distribution of contacts across the urban landscape. Our data have important implications for predicting the dynamics of contact-driven processes-particularly pathogen transmission-in urban raccoon populations.

  PublisherDOI

• Replication-incompetent VSV-based vaccine elicits protective responses against SARS-CoV-2 and influenza virus

  Science Advances · 2025-01-29 · 4 citations

  articleOpen access

  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses lead to severe respiratory illnesses and death in humans, exacerbated in individuals with underlying health conditions, remaining substantial global public health concerns. Here, we developed a bivalent replication-incompetent single-cycle pseudotyped vesicular stomatitis virus vaccine that incorporates both a prefusion-stabilized SARS-CoV-2 spike protein lacking a furin cleavage site and a full-length influenza A virus neuraminidase protein. Vaccination of K18-hACE2 or C57BL/6J mouse models generated durable levels of neutralizing antibodies, T cell responses, and protection from morbidity and mortality upon challenge with either virus. Furthermore, the vaccine provided heterologous protection upon challenge with a different influenza virus strain, supporting the advantage of using NA to increase the breadth of vaccine protection. Now, no bivalent vaccine is approved for use against both SARS-CoV-2 and influenza virus. Our study supports using this platform to develop safe and efficient vaccines against multiple viruses.

  PublisherDOI

• An outbreak of canine coronavirus type 2 in captive snow leopards (Panthera uncia) demonstrates a possible role for felids as mixing vessels for alphacoronaviruses

  IJID One Health · 2025-03-04 · 4 citations

  articleOpen accessSenior author

  <h2>Abstract</h2><h3>Objectives</h3> <i>Alphacoronavirus-1</i> comprises a set of viruses that are highly recombinogenic, including feline coronavirus (FCoV) type 2 (FCoV-2), a recombinant genotype of FCoV type 1, and canine coronavirus type 2 (CCoV-2). To understand the origin of novel recombinant variants, it is crucial to identify hosts susceptible to multiple alphacoronaviruses. The receptor for FCoV-2 and CCoV-2 is aminopeptidase N (APN), with the APN of the domestic cat allowing entry of FCoV-2 and CCoV-2. However, natural infection with CCoV-2 has been reported exclusively in canids. <h3>Methods</h3> We investigated an outbreak of CCoV-2 in captive snow leopards (<i>Panthera uncia</i>). We assessed the genetic diversity of the APN of five wild Asian felid species to evaluate their susceptibility to CCoV-2 and FCoV-2. <h3>Results</h3> The whole genome of CCoV-2 was sequenced from the feces of the snow leopards. It is closely related to pathogenic variants reported in domestic dogs in the United States and Europe. The APN of the wild felids is highly similar to the APN of the domestic cat. <h3>Conclusions</h3> This study provides the first genetic evidence of CCoV-2 infection in a felid and predicts that wild felids may be susceptible to FCoV-2 and CCoV-2. Therefore, felids may play a central role in the emergence of recombinant alphacoronavirus.

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• Enhanced RNA replication and pathogenesis in recent SARS-CoV-2 variants harboring the L260F mutation in NSP6

  PLoS Pathogens · 2025-03-31 · 4 citations

  articleOpen accessCorresponding

  The COVID-19 pandemic has been driven by SARS-CoV-2 variants with enhanced transmission and immune escape. Apart from extensive evolution in the Spike protein, non-Spike mutations are accumulating across the entire viral genome and their functional impact is not well understood. To address the contribution of these mutations, we reconstructed genomes of recent Omicron variants with disabled Spike expression (replicons) to systematically compare their RNA replication capabilities independently from Spike. We also used a single reference replicon and complemented it with various Omicron variant Spike proteins to quantify viral entry capabilities in single-round infection assays. Viral entry and RNA replication were negatively correlated, suggesting that as variants evolve reduced entry functions under growing immune pressure on Spike, RNA replication increases as a compensatory mechanism. We identified multiple mutations across the viral genome that enhanced viral RNA replication. NSP6 emerged as a hotspot with a distinct L260F mutation independently arising in the BQ.1.1 and XBB.1.16 variants. Using mutant and revertant NSP6 viral clones, the L260F mutation was validated to enhance viral replication in cells and increase pathogenesis in mice. Notably, this mutation reduced host lipid droplet content by NSP6. Collectively, a systematic analysis of RNA replication of recent Omicron variants defined NSP6's key role in viral RNA replication that provides insight into evolutionary trajectories of recent variants with possible therapeutic implications.

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• SARS-CoV-2 serosurvey of healthy, privately owned cats at a New York City animal hospital early in the COVID-19 pandemic (2020–2021)

  IJID One Health · 2025-09-17

  articleOpen accessSenior authorCorresponding

  We report a retrospective serological survey of cats presented to an animal practice in New York City, in close proximity to a medical center that treated the first wave of COVID-19 in the U.S. Using a bead-based multiplex assay, we sampled 79, mostly indoor cats between June 2020 and May 2021, the early part of which time the community was under a strict public health “lockdown”. We found an overall prevalence of 13/79 (16 %) serologically positive animals for the study period; however, cats sampled in the fall of 2020 had a confirmed positive prevalence of 44 %. Of the seropositive cats, 7/13 (54 %) were also positive by virus neutralization, and two seropositive cats had previously documented respiratory signs, with neutralization titers of 1:1024 and 1:4096. There was no statistically significant association of SARS-CoV-2 seropositivity with respiratory signs, or with breed, sex, or age of the animals. Follow-up sampling of cats showed that serological titers were maintained over time. We demonstrate the impact of SARS-CoV-2 in a defined feline population during the first wave of SARS-CoV-2 infection in humans and suggest that human-to-cat transmission was substantial in our study group. Our study provides a new One Health context for SARS-CoV-2 transmission events. • Cats were highly susceptible to SARS-CoV-2 early in the pandemic. • Results suggest concern for virus transmission from people to pets. • This study found the highest SARS-CoV-2 serology rate in U.S. cats to date. • The findings support routine virus surveillance in household pets.

  PublisherDOI

• Rethinking the drivers of coronavirus virulence and pathogenesis; toward an understanding of the dynamic world of mutations, indels, and recombination within the alphacoronaviruses

  mBio · 2025-08-28 · 4 citations

  reviewOpen accessSenior author

  , which comprises distinct viruses of cats, dogs, and pigs, along with a separate species that infects mustelids-as well as other related viruses of pigs and circulating human viruses. High-pathogenicity feline coronavirus (FCoV) is infamous as the cause of feline infectious peritonitis (FIP), existing as two distinct genotypes (types 1 and 2) and transmitted as a low-pathogenicity virus. The high-pathogenicity variants arise in cats infected with FCoV, and while the mutations responsible remain enigmatic, the main determinant is the spike glycoprotein. FCoV-1 disease outcome is driven by a combination of both within- and between-host evolution. Virulence can be largely explained by the "internal mutation hypothesis," which argues that high-pathogenicity-but poorly transmissible-variants are selected in individual cats. Canine coronaviruses are generally considered low pathogenicity but can cause severe enteritis and can be systemic. Notably, the canine coronavirus spike gene periodically recombines with FCoV-1 to generate FCoV-2, exemplified by FCoV-23, which has caused a widespread outbreak of FIP in Cyprus and has a notably truncated spike N-terminal domain (NTD). In pigs, coronaviruses often cause severe gastrointestinal disease but can become respiratory and have low pathogenicity based on what can also be considered an "internal deletion" of the spike NTD. These viruses may exist as a dynamic "metavirome" (the sum of all viral genomes present in a sample) that is in a constant state of flux, presenting notable challenges for disease surveillance and management.

  PublisherDOI

• Loss of FCoV-23 spike domain 0 enhances fusogenicity and entry kinetics

  Nature · 2025-07-09 · 15 citations

  articleOpen access

  . FCoV-23 is a recently emerged, highly pathogenic recombinant coronavirus responsible for a widespread outbreak of feline infectious peritonitis. Here we report cryogenic electron microscopy structures of two FCoV-23 spike isoforms that correspond to the in-host loss of domain 0 observed in clinical samples. The loss of domain 0 markedly enhances the fusogenicity and kinetics of entry into cells and possibly enables biotype switching and lethality. We show that FCoV-23 can use several aminopeptidase N orthologues as receptors and reveal the molecular determinants of receptor species tropism, including a glycan that modulates human receptor engagement. We define antigenic relationships among alphacoronaviruses that infect humans and other mammalian species and identify a cross-reactive alphacoronavirus monoclonal antibody that inhibits FCoV-23 entry. Our results pave the way for the development of vaccines and therapeutics that target this highly pathogenic virus.

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Recent grants

• NIH Grant R01AI048678

  NIH · $3.4M · 2014

• NIH Grant R21AI117300

  NIH · $457k · 2018

• NIH Grant R03AI060946

  NIH · $158k · 2006

• Structural and functional analysis of the coronavirus spike protein fusion peptide

  NIH · $2.5M · 2018–2023

• Development of a subunit vaccine for MERS-CoV and other emerging coronaviruses

  NIH · $432k · 2018–2021

Frequent coauthors

• Jean K. Millet

  Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

  110 shared

• Javier A. Jaimes

  New York University

  60 shared

• Nicole M. André

  49 shared

• Alison E. Stout

  New York University

  43 shared

• Marco R. Straus

  Cornell University

  40 shared

• Susan Daniel

  Cornell University

  39 shared

• Ximena A. Olarte‐Castillo

  36 shared

• Longping V. Tse

  Saint Louis University

  33 shared

Awards & honors

• Pfizer/Zoetis Animal Health Award for Research Excellence (2…