Host-Virus Interactions

Arboviruses are unique in that they require infection, replication and transmission from taxonomically diverse vertebrate and invertebrate hosts. Characterizing the complexity of these diverse interactions is critical to our understanding of arbovirus emergence and maintenance and is therefore among the primary research goals of the Wadsworth Center Arbovirus Laboratory.

West Nile virus is maintained primarily by Culex species mosquitoes and the focus of studies in this area is characterizing interactions in this system. Studies in recent years have begun to reveal the complexity and specificity of mosquito-virus interactions. Particular areas of interest include assessing temporal and spatial variability in vector competence, quantifying the effect of arbovirus infection on mosquito life history traits, identifying mechanisms of resistance, and characterizing interactions between arboviruses and the mosquito microbiome.

Dieme C, Kramer LD, Ciota AT. Vector competence of Anopheles quadrimaculatus and Aedes albopictus for genetically distinct Jamestown Canyon virus strains circulating in the Northeast United States. Parasit Vectors. 2022; 15 (1): 226. DOI: 10.1186/s13071-022-05342-3
Dieme C, Maffei JG, Diarra M, Koetzner CA, Kuo L, Ngo KA, Dupuis Ii AP, Zink SD, Backenson PB, Kramer LD, Ciota AT. Aedes Albopictus and Cache Valley virus: a new threat for virus transmission in New York State. Emerg Microbes Infect. 2022; 11 (1): 741-748. DOI: 10.1080/22221751.2022.2044733
Owen JC, Landwerlen HR, Dupuis AP 2nd, Belsare AV, Sharma DB, Wang S, Ciota AT, Kramer LD. Reservoir hosts experiencing food stress alter transmission dynamics for a zoonotic pathogen. Proc Biol Sci. 2021; 288 (1956): 20210881. DOI: 10.1098/rspb.2021.0881
Onyango MG, Attardo GM, Kelly ET, Bialosuknia SM, Stout J, Banker E, Kuo L, Ciota AT, Kramer LD. Zika Virus Infection Results in Biochemical Changes Associated With RNA Editing, Inflammatory and Antiviral Responses in Aedes albopictus. Front Microbiol. 2020; (11): 559035. DOI: 10.3389/fmicb.2020.559035
Gloria-Soria A, Payne AF, Bialosuknia SM, Stout J, Mathias N, Eastwood G, Ciota AT, Kramer LD, Armstrong PM. Vector Competence of Aedes albopictus Populations from the Northeastern United States for Chikungunya, Dengue, and Zika Viruses. Am J Trop Med Hyg. 2020; 104 (3): 1123-1130. DOI: 10.1186/s13071-020-04478-4
Dieme C, Ciota AT, Kramer LD. Transmission potential of Mayaro virus by Aedes albopictus, and Anopheles quadrimaculatus from the USA. Parasit Vectors. 2020; 13 (1): 613. DOI: 10.1186/s13071-020-04478-4
Ciota AT, Bialosuknia SM, Zink SD, Brecher M, Ehrbar DJ, Morrissette MN, Kramer LD. Effects of Zika Virus Strain and Aedes Mosquito Species on Vector Competence. Emerging Infectious Diseases. 2017; 23 (7): 1110-1117.
Ciota AT, Bialosuknia SM, Ehrbar DJ, Kramer LD. Vertical Transmission of Zika Virus by Aedes aegypti and Ae. albopictus Mosquitoes. Emerg Infect Dis. 2017; 23 (5): 880-882. DOI: 10.3201/eid2305.162041
Kilpatrick AM, Peters RJ, Dupuis AP, Jones MJ, Daszak P, Marra PP, Kramer LD. Predicted and observed mortality from vector-borne disease in wildlife: West Nile virus and small songbirds. Biological Conservation. 2013; 165 79-85.
Ciota AT, Chin PA, Kramer LD. The effect of hybridization of Culex pipiens complex mosquitoes on transmission of West Nile virus. Parasite Vectors. 2013; 6 (1): 305.
Ciota AT, Ehrbar DJ, Van Slyke GA, Payne AF, Willsey GG, Viscio RE, Kramer LD. Quantification of intrahost bottlenecks of West Nile virus in Culex pipiens mosquitoes using an artificial mutant swarm. Infection, Genetics & Evolution. 2012; 12 (3): 557-564.
Ciota AT, Styer LM, Meola MA and Kramer LD. The costs of infection and resistance as determinants of West Nile virus susceptibility in Culex mosquitoes. BMC Ecology. 2011; (11): 23.
Kilpatrick, AM, Fonseca, DM, Ebel, GD, Reddy, MR and Kramer, LD. Spatial and Temporal Variation in Vector Competence of Culex pipiens and Cx. restuans Mosquitoes for West Nile Virus. American Journal of Tropical Medicine & Hygiene. 2010; 83 (3): 607-613.

Arbovirus Evolution & Adaptation

Studies investigating the causes and consequences of genomic change of arboviruses are a focus of the Wadsworth Center Arbovirus Laboratory. Arboviruses are almost exclusively RNA viruses which replicate rapidly and are exceedingly error-prone. The resultant genetic diversity affords these pathogens vast evolutionary and adaptive potential that can have direct implications for their capacity to spread and cause human disease. Although arboviruses are often noted as being remarkably genetically stable, they are in fact in constant flux both within and among hosts.

Ongoing studies utilizing both natural virus isolates and laboratory-adapted strains combine traditional and next-generation sequencing and molecular tools with experimental infections and passaging to advance our understanding of evolutionary pressures and arbovirus fitness. Included in this are experimental evolution studies in both cell culture and natural hosts, phylogenetic studies assessing both geographic and temporal genetic change, studies assessing the phenotypic importance of intra-host diversity, and studies assessing host-specific selective pressures and the potential for host-range expansion. Although this work has focused on West Nile virus, additional studies have been completed or are ongoing with Zika virus, St. Louis encephalitis virus, Eastern equine encephalitis virus, Powassan virus, La Crosse virus and Dengue virus

Caldwell HS, Pata JD, Ciota AT. The Role of the Flavivirus Replicase in Viral Diversity and Adaptation. Viruses. 2022; 14 (5): 1076. DOI: 10.3390/v14051076
Bialosuknia SM, Dupuis Ii AP, Zink SD, Koetzner CA, Maffei JG, Owen JC, Landwerlen H, Kramer LD, Ciota AT. Adaptive evolution of West Nile virus facilitated increased transmissibility and prevalence in New York State. Emerg Microbes Infect. 2022; 11 (1): 988-999. DOI: 10.1080/22221751.2022.2056521
Ciota AT. Eastern Equine Encephalitis Virus Taxonomy, Genomics, and Evolution. J Med Entomol. 2022; 59 (1): 14-19. DOI: 10.1093/jme/tjab079
Kuo L, Jaeger AS, Banker EM, Bialosuknia SM, Mathias N, Payne AF, Kramer LD, Aliota MT, Ciota AT. Reversion to ancestral Zika virus NS1 residues increases competence of Aedes albopictus. PLoS Pathog. 2020; 16 (10): e1008951. DOI: 10.1371/journal.ppat.1008951
Caldwell HS, Ngo K, Pata JD, Kramer LD, Ciota AT. West Nile Virus fidelity modulates the capacity for host cycling and adaptation. J Gen Virol. 2020; 101 (4): 410-419. DOI: 10.1099/jgv.0.001393
Caldwell HS, Lasek-Nesselquist E, Follano P, Kramer LD, Ciota AT. Divergent Mutational Landscapes of Consensus and Minority Genotypes of West Nile Virus Demonstrate Host and Gene-Specific Evolutionary Pressures. Genes (Basel). 2020; 11 (11): 1299. DOI: 10.3390/genes11111299
Bialosuknia SM, Tan Y, Zink SD, Koetzner CA, Maffei JG, Halpin RA, Muller E, Novatny M, Shilts M, Fedorova NB, Amedeo P, Das SR, Pickett B, Kramer LD, Ciota AT. Evolutionary dynamics and molecular epidemiology of West Nile virus in New York State: 1999-2015. Virus Evol. 2019; 5 (2): vez020. DOI: 10.1093/ve/vez020
Tan Y, Lam TT, Heberlein-Larson LA, Smole SC, Auguste AJ, Hennigan S, Halpin RA, Fedorova N, Puri V, Stockwell TB, Shilts MH, Andreadis T, Armstrong PM, Tesh RB, Weaver SC, Unnasch TR, Ciota AT, Kramer LD, Das SR. Large-Scale Complete-Genome Sequencing and Phylodynamic Analysis of Eastern Equine Encephalitis Virus Reveals Source-Sink Transmission Dynamics in the United States. J Virol. 2018; 92 (12): e00074-18. DOI: 10.1128/JVI.00074-18
Van Slyke GA, Arnold JJ, Lugo AJ, Griesemer SB, Moustafa IM, Kramer LD, Cameron CE, Ciota AT. Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes. PLoS Pathogens. 2015; 11 (6): e1005009.

Impact of Temperature on Arbovirus Transmission

Among the most important consequences of climate change are alterations in patterns of pathogen transmission. Arboviruses and invertebrate vectors are particularly sensitive to the effects of temperature and therefore studies assessing the effects of temperature on viral and mosquito fitness are a focus of the Wadsworth Center Arbovirus laboratory.

Current areas of interest include quantifying species and population-specific effects of temperature on West Nile virus transmission in Culex mosquitoes and assessing the capacity for mosquito and virus populations to adapt to rising temperatures. Experimental data are combined with surveillance and climate data to inform novel predictive transmission models. The overarching goal of these studies is to gain insight into how changing climates alter arbovirus risk and ultimately use these data to inform public health measures.

Fay RL, Keyel AC, Ciota AT. West Nile virus and climate change. In: Roossinck MJ, editor. Viruses and Climate Change, Advances in Virus Research. Cambridge, MA: Academic Press. 2022; DOI: 10.1016/bs.aivir.2022.08.002
Onyango MG, Lange R, Bialosuknia S, Payne A, Mathias N, Kuo L, Vigneron A, Nag D, Kramer LD, Ciota AT. Zika virus and temperature modulate Elizabethkingia anophelis in Aedes albopictus. Parasit Vectors. 2021; 14 (1): 573. DOI: 10.1186/s13071-021-05069-7
Fay RL, Ngo KA, Kuo L, Willsey GG, Kramer LD, Ciota AT. Experimental Evolution of West Nile Virus at Higher Temperatures Facilitates Broad Adaptation and Increased Genetic Diversity. Viruses. 2021; 13 (10): 1889. DOI: 10.3390/v13101889
Keyel AC, Raghavendra A, Ciota AT, Elison Timm O. West Nile virus is predicted to be more geographically widespread in New York State and Connecticut under future climate change. Glob Chang Biol. 2021; 27 (21): 5430-5445. DOI: 10.1111/gcb.15842
Onyango MG, Bialosuknia SM, Payne AF, Mathias N, Kuo L, Vigneron A, DeGennaro M, Ciota AT, Kramer LD. Increased temperatures reduce the vectorial capacity of Aedes mosquitoes for Zika virus. Emerg Microbes Infect. 2020; 9 (1): 67-77. DOI: 10.1080/22221751.2019.1707125
Ciota AT, Keyel AC. The Role of Temperature in Transmission of Zoonotic Arboviruses. Viruses. 2019; 11 (11): 1013. DOI: 10.3390/v11111013
Ciota AT, Chin PA, Ehrbar DJ, Micieli MV, Fonseca DM, Kramer LD. Differential Effects of Temperature and Mosquito Genetics Determine Transmissibility of Arboviruses by Aedes aegypti in Argentina. Am J Trop Med Hyg. 2018; 99 (2): 417-424. DOI: 10.4269/ajtmh.18-0097
Ciota AT, Matacchiero AC, Kilpatrick AM, Kramer LD. The effect of temperature on life history traits of Culex mosquitoes. Parasite Vectors. 2014; 51 (1): 55-62.


Despite the global disease burden associated with arboviruses, there are very few therapeutics approved for the treatment of arboviral infections. The Arbovirus Laboratory is involved in testing novel antiviral compounds, including toxicity and efficacy studies against a range of arboviruses including: West Nile virus, dengue virus, Powassan virus, Zika virus, and chikungunya virus. These studies are performed both on cell culture and using vertebrate models of disease.

Passow KT, Caldwell HS, Ngo KA, Arnold JJ, Antczak NM, Narayanan A, Jose J, Sturla SJ, Cameron CE, Ciota AT, Harki DA. A Chemical Strategy for Intracellular Arming of an Endogenous Broad-Spectrum Antiviral Nucleotide. J Med Chem. 2021; 64 (20): 15429. DOI: 10.1021/acs.jmedchem.1c01481
Li Z, Lang Y, Sakamuru S, Samrat S, Trudeau N, Kuo L, Rugenstein N, Tharappel A, D'Brant L, Koetzner CA, Hu S, Zhang J, Huang R, Kramer LD, Butler D, Xia M, Li H. Methylene blue is a potent and broad-spectrum inhibitor against Zika virus in vitro and in vivo. Emerg Microbes Infect. 2020; 20 1-37. DOI: 10.1080/22221751.2020.1838954
Li Z, Xu J, Lang Y, Fan X, Kuo L, D'Brant L, Hu S, Samrat SK, Trudeau N, Tharappel AM, Rugenstein N, Koetzner CA, Zhang J, Chen H, Kramer LD, Butler D, Zhang QY, Zhou J, Li H. JMX0207, a Niclosamide Derivative with Improved Pharmacokinetics, Suppresses Zika Virus Infection Both In Vitro and In Vivo. ACS Infect Dis. 2020; 6 (10): 2616-2628. DOI: 10.1021/acsinfecdis.0c00217
Kim SY, Koetzner CA, Payne AF, Nierode GJ, Yu Y, Wang R, Barr E, Dordick JS, Kramer LD, Zhang F, Linhardt RJ. Glycosaminoglycan Compositional Analysis of Relevant Tissues in Zika Virus Pathogenesis and in Vitro Evaluation of Heparin as an Antiviral against Zika Virus Infection. Biochemistry. 2019; 58 (8): 1155-1166. DOI: 10.1021/acs.biochem.8b01267

Tick-borne Virus Surveillance and Research

New York State is a major focus of tick-borne pathogens. The etiologic agents responsible for Lyme disease, Anaplasmosis, Babesiosis, and Powassan encephalitis are transmitted by Ixodes scapularis (black-legged or “deer” ticks). The ticks and pathogens they transmit are expanding north- and west-ward from the original epicenter of the lower Hudson River Valley. Recently, Amblyomma americanum (lone-star) ticks have been expanding their range from the southeastern and midwestern United States and into Long Island and southern NYS. This tick is capable of transmitting the agent responsible for Ehrlichiosis as well as Heartland and Bourbon Viruses.

The Arbovirus Laboratory has partnered with the Bureau of Communicable Disease Control to establish a surveillance and research program to understand the geographic distribution of Powassan (Deer Tick virus, DTV), Heartland, and Bourbon viruses in NYS by testing ticks collected in the spring and fall each year and testing vertebrate sera for the presence of antibody. The laboratory has documented DTV throughout the Hudson River Valley, determined co-infection rates of DTV and bacterial pathogens in adult and nymphal ticks collected in Dutchess and Putnam Counties, and has led to the discovery of novel viral agents in ticks collected across NYS. In 2018 and 2019 respectively, the laboratory documented Heartland and Bourbon viruses in ticks collected on Long Island, NY, representing the first time these pathogens have been isolated outside the known endemic areas of the Midwest. The Arbovirus Laboratory’s tick research and surveillance component complements our proficient mosquito-borne virus program.

Dupuis AP 2nd, Prusinski MA, O'Connor C, Maffei JG, Ngo KA, Koetzner CA, Santoriello MP, Romano CL, Xu G, Ribbe F, Campbell SR, Rich SM, Backenson PB, Kramer LD, Ciota AT. Heartland Virus Transmission, Suffolk County, New York, USA. Emerg Infect Dis. 2021; 27 (12): 3128-3132. DOI: 10.3201/eid2712.211426
Frost HM, Schotthoefer AM, Thomm AM, Dupuis AP 2nd, Kehl SC, Kramer LD, Fritsche TR, Harrington YA, Knox KK. Serologic Evidence of Powassan Virus Infection in Patients with Suspected Lyme Disease. Emerg Infect Dis. 2017; 23 (8): 1384-1388. DOI: 10.3201/eid2308.161971
Aliota MT, Dupuis AP, Wilczek MP, Peters RJ, Ostfeld RS, Kramer LD. The Prevalence of Zoonotic Tick-Borne Pathogens in Ixodes Scapularis Collected in the Hudson Valley, New York State. Vector Borne Zoonotic Diseases. 2014; 14 (4): 245-250.
Dupuis AP, Peters RJ, Prusinski MA, Falco RC, Ostfeld RS, Kramer LD. Isolation of deer tick virus (Powassan virus, lineage II) from Ixodes scapularis and detection of antibody in vertebrate hosts sampled in the Hudson Valley, New York State. Parasite & Vectors. 2013; (6): 185.