Biology subjects

Damodaran, L.

Publications and source records attributed to Damodaran, L..

7 recordsLinked to original sources

bioRxiv2026

Host type governs influenza evolutionary strategy across reservoir and spillover hosts

Despite its high propensity for host switching, the evolutionary mechanisms underlying influenza host adaptation remain unclear. H3Nx influenza viruses are uniquely generalist, with long-term lineages that circulate in avian, human, swine, equine, and canine hosts. Using 13,295 H3Nx sequences, we quantified host-specific adaptive evolution and developed a pipeline to map reassortment events onto trees with measures of statistical uncertainty. We find that while H3Nx viruses in mammals undergo adaptive evolution in HA and NA, viruses in birds experience very little directional selection. Instead, avian lineages exhibit high rates of reassortment, frequently generating novel reassortant lineages that persist transiently and turn over rapidly. 29.8-47.4% of all avian reassortant lineages are purged within the first year of circulation, and reassortment shows no fitness benefit in birds. In contrast, reassorted lineages in swine are more likely to persist long-term, suggesting that reassortment in swine may be broadly beneficial. Segment-specific reassortment patterns were also distinct between avian and mammalian viruses, with NA reassorting more frequently than expected in birds, but less frequently than expected in swine. Reassortment events are enriched between mammalian, but not avian, host switches, suggesting that reassortment may be most beneficial for mediating host switches among mammalian species. Together, our data suggest that host differences drive fundamentally different evolutionary outcomes for influenza viruses, transitioning from reassortment-dominant evolution in their avian reservoir, to varying degrees of adaptation upon establishment in mammals.

evolutionary biology↗

bioRxiv2026

Molecular and ecological determinants of effective reassortment in orthohantaviruses

A central unsolved problem in RNA virus evolution is understanding why some viral reassortants establish and persist while others do not. To answer this question, we reconstructed reassortant histories across 553 viral genomes from seven orthohantavirus species between 1983 and 2024 using phylogenetic reconciliation and molecular dating. We found that the frequency of retained reassortants varied among orthohantaviruses. For example, reassortment ranged from absent in Andes virus to frequent in Dobrava-Belgrade, Sin Nombre, Seoul, Puumala, and Tula viruses, showing that effective reassortment is not a genus-wide constant. Our Bayesian hierarchical models identified local host overlap as the strongest ecological factor associated with viral reassortment, while cross-segment linkage and terminal RNA structure serve as a molecular filter. We found that the probability of reassortment establishment is highest when ecological opportunity is paired with molecular permissiveness, with their interaction term inferred as the strongest signal in our establishment models (posterior probability = 0.97). These results suggest that reassortment in orthohantaviruses is a sequentially filtered evolutionary process in which divergent lineages must first meet in a host through ecological overlap, exchange segments that are molecularly compatible, and do so within a lineage background permissive to establishment in the host population.

evolutionary biology↗

bioRxiv2026

Frequent seasonal reassortment between high and low path viruses drives the diversification of influenza A/H5N1

Since 2021, highly pathogenic (HPAI) H5N1 viruses have spread across the Americas, diversifying via reassortment into new genotypes that have spilled into humans and livestock, raising fears of a new influenza pandemic. Pandemic lineages are typically associated with reassortment, but we currently have limited understanding of where and when reassortment is expected to occur, which limits our ability to assess pandemic risks. Using a dataset of 9,052 full-genome sequences, we show that reassortment and novel genotype formation are associated with seasonal variation in low pathogenicity avian influenza (LPAI) cases and with the spatial and host distributions of viral transmission. We pinpoint ducks, geese, and the Central flyway as frequent sources of new genotypes, and show that reassortment rates vary seasonally, driven by mixing between high- and low-pathogenicity viruses. Cattle spillover genotypes (B3.13 and D1.1) evolved during periods of high reassortment, implicating reassortment as a common occurrence in lineages evolving during particular time periods. Together, these findings reframe reassortment as a predictable ecological process, with direct implications for how surveillance and pandemic risk assessment should be designed.

evolutionary biology↗

bioRxiv2024

Intensive transmission in wild, migratory birds drove rapid geographic dissemination and repeated spillovers of H5N1 into agriculture in North America

Since late 2021, a panzootic of highly pathogenic H5N1 has devastated wild birds, agriculture, and mammals. Analysis of 1,818 Hemagglutinin sequences from wild birds, domestic birds and mammals revealed that the North American panzootic was driven by [~]9 introductions into the Atlantic and Pacific Flyways, followed by rapid dissemination via wild, migratory birds. Transmission was primarily driven by Anseriformes, while non-canonical species acted as dead-end hosts. Unlike the epizootic of 2015, outbreaks in domestic birds were driven by [~]46-113 independent introductions from wild birds that persisted for up to 6 months. Backyard birds were infected [~]9 days earlier on average than commercial poultry, suggesting potential as "early warning signals" for transmission upticks. We find that wild birds are an emerging source of H5N1 in North America, necessitating enhanced, continuous surveillance. Prevention of agricultural outbreaks may now require novel strategies that reduce transmission at the wild bird/agriculture interface.

ecology↗

bioRxiv2024

The Evolution and Epidemiology of H3N2 Canine Influenza Virus After 20 Years in Dogs

The H3N2 canine influenza virus (CIV) emerged from an avian reservoir in Asia around 2004. As the virus has now been circulating entirely among dogs for 20 years, we here update our understanding of the evolution of virus in its new host. As a host-switched virus, H3N2 CIV will also reveal any host-adaptive changes arising during thousands of infections within its new host, and our analysis showed that the virus has evolved at a constant rate. CIV was first introduced into North America in 2015 from Korea, and we specifically examined the epidemiology of the virus among dogs in North America since then, including local outbreaks, regional die-outs, and repeated reintroduction from Asia. The H3N2 CIV now appears endemic only in China after dying out in South Korea around 2017. Virus lineages circulating in China appear to have seeded the most recent US outbreaks - with 2 or 3 introductions into North America during the past 3 years. Combining clinical reports, diagnostic testing data, and analysis of viral genomes we show that the virus spreads rapidly among dogs in kennels and shelters in different regions - likely dying out locally after all those animals become infected and immune. The overall epidemic therefore requires longer-distance dispersal of virus to initiate outbreaks in new locations. Patterns of spread in the USA may select viruses most adapted to those dense populations, which may lack the properties required for efficient long-distance transfers to other dog populations that would keep the virus in prolonged circulation. IMPORTANCEViruses occasionally jump into new hosts to cause epidemics and may spread widely due to movement of humans or animals, or their viruses, with profound consequences for global health. The emergence and epidemiology of new epidemic viruses in companion animals provides a model for understanding disease dynamics and evolution. The H3N2 canine influenza virus arose from an avian virus, and infected dogs provide many opportunities for human exposure. H3N2 CIV transmission is dominated by fast-moving outbreaks within dense populations in animal shelters or kennels, while sustaining the epidemic likely requires movement of virus to more distant dog populations. Viral spread within North Americahas only been sustained for a few years at a time after which the virus dies out. The epidemiological and evolutionary dynamics of this virus in this structured host population shows how an acute respiratory pathogen can emerge and spread in a new host and population.

microbiology↗

bioRxiv2024

Pandemic Risk Assessment for a Swine Influenza A Virus in Comparative Human Substrates

Swine influenza A viruses pose a public health concern as novel and circulating strains occasionally spill over into human hosts, with the potential to cause disease. Crucial to preempting these events is the use of a threat assessment framework for human populations. However, established guidelines do not specify what animal models or in vitro substrates should be used. We completed an assessment of a contemporary swine influenza isolate, A/swine/GA/A27480/2019, using animal models and human cell substrates. Infection studies in vivo revealed high replicative ability and a pathogenic phenotype in the swine host with replication corresponding to a complementary study performed in swine primary respiratory epithelial cells. However, replication was limited in human primary cell substrates. This contrasted with our findings in the Calu-3 cell line, which demonstrated a replication profile on par with the 2009 pandemic H1N1 virus. These data suggest selection of models is important for meaningful risk assessment. Article Summary LineA novel swine influenza A virus was rigorously assessed for pandemic potential in animal models and human surrogate culture models, illustrating a wide range in potential public health risk dependent on the model utilized.

microbiology↗

bioRxiv2020

Comparison of the knockdown resistance locus (kdr) in Anopheles stephensi, An. arabiensis, and Culex pipiens s.l. suggests differing mechanisms of pyrethroid resistance in east Ethiopia

The malaria vector, Anopheles stephensi, which is typically restricted to South Asia and the Middle East, was recently detected in the Horn of Africa. Controlling the spread of this vector could involve integrated vector control that considers the status of insecticide resistance of multiple vector species in the region. Previous reports indicate that the knockdown resistance mutations (kdr) in the voltage-gated sodium channel (vgsc) are absent in both pyrethroid resistant and sensitive variants of An. stephensi in east Ethiopia but similar information on other vector species in the same areas is limited. In this study, kdr and the neighboring intron was analyzed in An. stephensi, An. arabiensis, and Culex pipiens s. l. collected in east Ethiopia between 2016 and 2017. Sequence analysis revealed that all of Cx. pipiens s.l. (n = 42) and 71.6% of the An. arabiensis (n=67) carried kdr L1014F known to confer target-site pyrethroid resistance. Intronic variation was only observed in An. stephensi (segregating sites = 6, haplotypes = 3) previously shown to have no kdr mutations. In addition, no evidence of non-neutral evolutionary processes was detected at the An. stephensi kdr intron which further supports target-site mechanism not being a major resistance mechanism in this An. stephensi population. Overall, these results suggest differences in evolved mechanisms of pyrethroid/DDT resistance in populations of vector species from the same region. Variation in insecticide resistance mechanisms in East Ethiopian mosquito vectors highlight possible species or population specific biological factors and distinct environmental exposures that shape their evolution.

evolutionary biology↗