Influenza D virus, a pathogen best known for causing respiratory illness in cattle, appears to be silently infecting farmworkers across multiple continents, according to a growing body of serological evidence. Unlike its better-known relatives influenza A and B, which drive seasonal epidemics, influenza D (IDV) is not currently monitored in human populations and has no vaccine. With new laboratory data showing the virus replicates efficiently in human airway tissue, and with antibody rates among cattle workers reaching as high as 97% in some studies, the question facing public health authorities is no longer whether IDV can jump to people, but how often it already does.
Cattle Workers Show Striking Antibody Rates
Two peer-reviewed serology studies, conducted years apart on different continents, point to the same conclusion: people who work closely with cattle carry IDV antibodies at rates far above those of the general population. A cross-sectional study in north-central Florida found that cattle-exposed adults tested positive at roughly 91% by hemagglutination inhibition (HI) and 97% by microneutralization (MN), compared with just 18% MN positivity among non-exposed controls. Those numbers, in a setting where participants reported routine contact with dairy and beef herds, suggest repeated, unrecognized exposure rather than a single chance encounter and imply that IDV may be behaving like an occupational hazard similar to other zoonotic respiratory viruses.
A more recent occupational health study sampled cattle workers in Southern Italy during 2023 and 2024, testing for antibodies against two distinct IDV lineages, D/660 and D/OK. According to that research, 42.9% of cattle workers tested positive to at least one lineage, with 39.3% positive to D/660 and 34.3% positive to D/OK. The study included a local control group with substantially lower seroprevalence, reinforcing that the elevated rates are tied to occupational contact rather than background community exposure. Taken together, these datasets from Florida and Southern Italy establish that IDV is not a theoretical human threat. It is already crossing the species barrier in farm settings, likely in the form of mild or unrecognized infections that standard clinical testing would miss.
IDV Thrives in Human Airway Tissue
Antibody evidence alone cannot prove that IDV causes productive infection in people, because antibodies may occasionally reflect exposure to related antigens or cross-reactive immune responses. A recent preprint directly addressed that gap by exposing human respiratory tissue models to a panel of IDV isolates collected from cattle and swine between 2011 and 2020. The virus replicated efficiently in those human airway cell systems, reaching titers comparable to influenza A virus in side-by-side comparisons and infecting both upper and lower airway cell types. That finding matters because efficient replication in human tissue is one of the key prerequisites virologists look for when assessing pandemic potential, alongside factors such as transmissibility and population immunity.
No one has yet isolated IDV directly from a human respiratory sample, which remains a significant gap in the evidence and limits the ability to link the virus to specific clinical syndromes. However, the combination of high seroprevalence in cattle workers and strong replication in lab-grown human airways suggests that mild or asymptomatic infections could be occurring and going undetected, especially in rural areas where viral diagnostics are sparse. A parallel situation has already played out with avian influenza. Serologic surveys of dairy workers exposed to highly pathogenic H5 viruses have identified individuals with antibodies despite little or no reported illness, indicating that subclinical zoonotic infections can be more common than recognized. If silent spillovers can happen with H5 under active surveillance, there is little reason to assume IDV behaves differently in the absence of routine testing.
A Virus With a Very Wide Host Range
One reason IDV warrants attention beyond its cattle-worker footprint is the sheer breadth and intensity of its animal reservoir. A national serosurvey of 1,992 bovine sera collected in 2014 and 2015 found 77.5% seropositivity across the United States, with broad geographic distribution spanning multiple states and regions. That level of saturation means virtually any cattle operation in the country could serve as a site of potential human exposure, particularly for workers involved in calving, milking, and veterinary procedures that generate respiratory aerosols. In such an environment, IDV can circulate continuously in herds, creating repeated opportunities for the virus to encounter human airways.
The virus does not stop at cattle. A large multi-species serology dataset from Italy identified cattle as the primary reservoir while also documenting IDV antibodies in swine and wildlife, including wild boars, based on animal sampling across multiple regions. Separate multi-species sampling in Ukraine, covering collections from 2021, 2023, and 2024 totaling 363 sera across several species, found substantial seroprevalence in horses, measurable prevalence in swine, and sporadic positives in wild and companion animals. This geographic and species diversity raises a specific concern: when a virus circulates in cattle, pigs, and horses simultaneously on the same farms or trading networks, the chance of reassortment (where viral gene segments swap to create new variants) increases. That mechanism is exactly how pandemic influenza A strains have emerged in the past, turning multi-host systems into evolutionary “mixing vessels.”
Reassortment Signals in Circulating Strains
Molecular surveillance is already picking up signs of IDV genetic mixing that are consistent with this multi-host ecology. A retrospective screening of 1,763 bovine respiratory samples from Sweden, collected between January 2021 and June 2024, identified IDV-positive specimens and subjected those with the strongest viral loads to whole-genome sequencing. Phylogenetic analysis revealed evidence of multiple clades and reassortant viruses circulating across different years, indicating that exchange of genome segments is not a rare event, but an ongoing feature of IDV evolution in cattle. That pattern mirrors what influenza A does in swine populations before occasionally producing variants capable of infecting humans, underscoring that genetic innovation in animal hosts can have downstream implications for people.
These reassortment signals matter because they expand the theoretical space of IDV phenotypes that could eventually encounter humans. A reassorted virus might acquire changes in surface proteins that alter receptor binding, or internal gene constellations that enhance replication in mammalian airways, even if most such combinations remain confined to livestock. At present, there is no evidence that any specific IDV lineage has adapted for efficient human-to-human transmission, and no confirmed human respiratory isolates have been reported. Nonetheless, the Swedish data demonstrate that the virus is actively experimenting at the genetic level in large cattle populations. This increases the odds that a variant with improved human fitness could emerge, particularly in settings where humans, cattle, and other susceptible species interact closely.
Surveillance Gaps and Policy Implications
Despite these warning signs, IDV remains largely absent from routine human or veterinary surveillance, creating blind spots that make it difficult to assess risk in real time. Most respiratory panels used in hospitals and clinics do not include IDV targets, meaning even symptomatic human infections would likely be misclassified as generic viral illness or seasonal influenza A or B. On the animal side, many countries focus influenza testing on avian and swine populations for trade and outbreak-control reasons, while cattle respiratory disease is often managed syndromically without systematic virologic workups. This fragmented picture contrasts sharply with the extensive genomic and epidemiologic monitoring now applied to avian H5 viruses and to some swine influenza lineages.
Closing these gaps would not require building entirely new systems from scratch. Instead, public health agencies and veterinary services could integrate IDV into existing “One Health” frameworks that already coordinate surveillance across human, animal, and environmental sectors. Practical steps might include adding IDV assays to respiratory multiplex panels in sentinel hospitals near dense cattle regions, incorporating IDV testing into routine bovine respiratory disease investigations, and archiving positive animal samples for genomic sequencing to track reassortment and lineage spread. Occupational health programs for farmworkers could also pilot periodic serosurveys and targeted education on respiratory protection, especially in high-prevalence settings such as large dairies and feedlots.
Policy decisions will ultimately hinge on how much risk societies are willing to tolerate from a virus that, so far, appears to cause mostly mild disease in its primary hosts but shows clear signs of human exposure and robust replication in human tissues. Investing early in surveillance and risk assessment would allow authorities to detect any shift in IDV behavior (such as the appearance of confirmed human cases, evidence of limited human-to-human transmission, or emergence of highly divergent reassortant strains) before the virus has a chance to spread widely. In that sense, influenza D offers an opportunity to apply lessons from past influenza and coronavirus threats: treat repeated animal-to-human contact, high seroprevalence in workers, and active genetic diversification as prompts for proactive monitoring rather than as curiosities to be revisited only after a crisis has begun.
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*This article was researched with the help of AI, with human editors creating the final content.
