#18,790
In June of last year we saw - for the very first time - mice (Mus musculus aka the common house mouse) added to the USDA's list of wild mammals detected with H5N1 in the United States (see USDA Adds House Mouse To Mammals Affected by H5N1).
This was somewhat unexpected, as wild mice naturally express Mx1 - a resistance factor that significantly reduces (but doesn't entirely eliminate) their susceptibility to influenza A viruses - which is why genetically altered Mx1- (deficient) mice are often used in influenza research.
Since then, more than 1/3rd of all H5 infected wildlife reported to the USDA (132 out of 384) have come from mice (n=124) or rats (n=8), many of which were recovered in or near infected dairy farms.
Last September we looked at two studies which challenged previously held assumptions (see 2007's Mx1 gene protects mice against the highly lethal human H5N1 influenza virus):
- First, in Emer. Microbe & Inf.: HPAI Virus H5N1 clade 2.3.4.4b in Wild Rats in Egypt during 2023, we a surprisingly high percentage of wild rats testing positive for H5 antibodies in Egypt.
- A second, a study in Pathogens (Susceptibility of Synanthropic Rodents to H5N1 Subtype HPAI Viruses), where researchers challenged several rodent species (house mice, brown rat, black rat) with two (older 2010, 2007) HPAI H5N1 viruses, and found they are both susceptible to the virus and could potentially play a role it its evolution and spread.
Today we've a new study, specifically focused on the susceptibility and shedding of Bovine (genotype B3.13) H5N1 in both Mx1+ and Mx1- laboratory mice, that finds both are susceptible to the virus, and both excrete the virus in their urine.
It is worth noting that exposure to mouse/rat urine and/or dropping is often associated with transmission of many zoonoses, including hantaviruses, leptospirosis, Tularemia, and Lassa fever (see Viruses Review - The Hidden Threat: Rodent Borne Diseases).
While many will want to read the full open access report, I've posted the link and some excerpts below. I'll have a bit more after the break.
Asim Biswasa,f ∙ Amie J. Eisfelda,f ∙ Lizheng Guana ∙ Chunyang Gua ∙ Tong Wanga ∙ Hassanein H. Abozeida,e ∙ et al. Show more
Summary
Background
Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses have spread prolifically in dairy cattle in the US, resulting in dozens of human infections, some without well-established links to animal contacts. Many wild mammals have also been affected, including peridomestic house mice.
Methods
Here, we evaluated susceptibility, tissue tropism, and shedding in female PWK/PhJ and BALB/cJ mice, two laboratory strains derived from house mice that differ in expression of the antiviral restriction factor Mx1. PWK/PhJ mice, which were selected for their natural expression of Mx1, better reflect the antiviral capacity of most wild house mice, whereas BALB/cJ mice lack functional Mx1.
Findings
We found that, regardless of Mx1 expression status, mice are susceptible to infection by dairy cattle HPAI H5N1 viruses, that infection leads to systemic spread to non-respiratory sites, and that infected animals shed virus into the environment via urine. Shed virus remained infectious in urine for at least 24 h at room temperature.
Interpretation
These findings suggest that wild house mice could contribute to HPAI H5N1 environmental contamination and may play a role in transmission to other hosts.
Funding
This work was supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Response (contract 75N93021C00014) and by grants from the Japan Agency for Medical Research and Development (JP25wm0125002, JP253fa627001, and JP24fk0108626, to Y.K.).
Research in context
Evidence before this study
The recent outbreak of highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses in dairy cattle has led to multiple human infections and the first reported HPAI H5N1-related death in the United States, according to the CDC. Surveillance data reported by the USDA has also identified infections in several wild mammal species, including wild house mice, which frequently live near humans and livestock. Previous studies have shown that laboratory mice lacking the influenza restriction gene Mx1 are susceptible to infection with HPAI H5N1 from dairy cattle. However, it remains unclear whether mice with a functional Mx1 gene—such as those found in wild populations—can support viral replication and shed virus in ways that might contribute to transmission risk.
Added value of this study
We demonstrate that mice naturally expressing a functional Mx1 gene are susceptible to infection with dairy cattle-derived HPAI H5N1. The virus disseminated systemically, was shed in urine, and remained infectious in urine for at least 24 h at room temperature. These findings suggest that wild mice may contribute to environmental contamination and could potentially play a role in interspecies transmission.
Implications of all the available evidence
Although the role of rodents in the spread of HPAI H5N1 is not yet fully understood, our findings provide experimental evidence that wild-derived mice expressing Mx1 can become infected, develop severe disease, and shed infectious virus. These results support the need for further investigation into the contribution of wild rodents to HPAI H5N1 transmission on farms and suggest that rodent control may be an important component of biosecurity strategies.
Surveillance for HPAI in wildlife in the United States - and the rest of the world - is mostly passive, and relies both on a combination of luck and a willingness of local authorities to report and/or test dead animals.
The USDA map of HPAI H5 detections since early 2022 (below) suggests that some states may be looking harder than others. Indeed, some states have yet to report a single finding.
Admittedly, many animals die unseen in remote swamps, forests, or deserts while others may recover, escaping detection (see Emerg. Microb. & Inf.: High Number of HPAI H5 Virus Infections & Antibodies in Wild Carnivores in the Netherlands , 2020–2022).
Even the most aggressive jurisdictions are apt to miss the vast majority of infections in the wild. We are undoubtedly only seeing the tip of the iceberg.
We have seen a few studies where researchers have proactively sampled rodents, shrews, and voles in the wild for novel, or zoonotic, viruses.
- In 2015's Taking HPAI To The Bank (Vole) found this European mammal was susceptible to two types of avian flu viruses (H5N1 & H7N1), most were able to carry the virus asymptomatically, shed the virus in copious amounts, and were able to pass on the virus to naïve co-housed sentinel voles.
- A 2019 study out of Boston found RT-PCR evidence of IAV (Influenza A Virus) in 11% of 163 Norway rats (Rattus norvegicus) trapped and swabbed (note: half came from paw swabs, which may indicate contamination rather than infection).
- And just last year, in Nature: Decoding the RNA Viromes in Shrew Lungs Along the Eastern Coast of China - we looked at a study that found a wide range of zoonotic viruses - including HPAI H5N6 - in shrews.
Sadly, nearly 4 years into this North American HPAI epizootic we know surprisingly little about the ecology of H5Nx in mammalian wildlife, and whether they are capable of spreading these viruses to livestock, pets, and even humans.
And if we aren't actively looking, we'll never see it coming.