Sunday, May 10, 2026

Sci Adv: Mammary and Respiratory Infection of Sheep with H5Nx clade 2.3.4.4b Viruses with Milk-mediated Transmission to Lambs

 

#19,154

While we await further news on the offloading of hantavirus exposed passengers from the m/v Hondius, we still have plenty of older and emerging threats to keep our eye on.  Late last week a new study was published in Science Advances by Canadian researchers who investigated the susceptibility of sheep to both HPAI H5N1 and HPAI H5N5. 

Since the first outbreak of HPAI H5N1 was reported in U.S. dairy cattle a little over 2 years ago, surveillance and testing of mammalian livestock has focused almost exclusively on lactating dairy cows.

Yet during this time, we've also seen sporadic HPAI spillovers into goats, alpacas, pigs, and sheep in the UK and the discovery of  H5N1 antibodies in sheep in Norway. Other non-bovine findings include:

Transboundary & Emerg Inf: Serological Evidence of HPAI (H5N1) in Invasive Wild Pigs in Western Canada,

Preprint: Highly Pathogenic Avian Influenza H5 Virus Exposure in Goats and Sheep (in Pakistan).

EID Journal: Evidence of Influenza A(H5N1) Spillover Infections in Horses, Mongolia
Livestock surveillance - even of cattle - remains passive and limited, despite the call from animal health authorities (see WOAH Statement (Oct 22nd): High Pathogenicity Avian Influenza (HPAI) in Cattle) to increase vigilance. 

Although cattle-centric, WOAH does refer to `cattle and other livestock populations' in their messaging, but until now spillovers into sheep, goats, and other non-bovie ruminants have been often dismissed as either rare or dead end infections.

Today's study illustrates that small ruminants are not only susceptible to HPAI H5 infections; there is the potential for `widespread virus transmission within flocks'.  

The authors discuss the need for increased surveillance and the implementation of stricter biosecurity measures, particularly in mixed-species environments.

First the link, abstract, and some excerpts from a much longer study.  Follow the link to read it in its entirety.  I'll have a bit more after the break.  

 

H5Nx clade 2.3.4.4b viruses are evolving rapidly, expanding host ranges and threatening animal and public health. In the US, genotype B3.13 dominates dairy outbreaks, while D1.1 is linked to fewer cases. In the UK, an asymptomatic ewe infected with genotype DI.2 raised concerns about ruminant susceptibility.
We inoculated lactating and nonlactating sheep with D1.1 (H5N1) and A6 (H5N5) viruses. Intramammary inoculation in lactating sheep caused clinical mastitis, high viral loads in milk, and transmission to suckling lambs, which further spread infection to the uninoculated mammary glands. Both ewes and their lambs seroconverted.
Aerosol exposure of nonlactating sheep led to transient respiratory infection, with low-level viral replication, and seroconversion. In vitro, both viruses replicated in sheep mammary epithelial cells.
These findings establish sheep as a viable ruminant model for H5N1 and H5N5 infection and highlight previously unidentified transmission dynamics, including milk-mediated and lamb-to-ewe spread, relevant for surveillance and biosecurity in ruminant populations.

        (SNIP)

Deep sequencing of milk samples from mammary glands, oral swabs, and lung tissues revealed the emergence of viral variants distinct from the consensus sequence generated from the challenge D1.1 virus.

Notably, the left mammary gland of a D1.1-infected sheep appeared to select for the variant PB2-701N, while the right gland retained mixed residues of PB2-627 (E/K) and PB2-701 (D/N). Sequence analysis suggests that the PB2-D701N mutation arose before transmission to the left gland, as oral swab from one suckling lamb already carried this mutation.

Dairy cows experimentally infected with H5N1 via the intramammary route acquired PB2-E627K mutation (32). While D1.1 viruses from some dairy cases exhibited the mammalian adaptive mutation PB2-D701N, the genotype B3.13 from all dairy cases retained the bovine-specific PB2-M631L mutation (74). Both PB2-E627K and PB2-D701N provide IAVs with significant replication advantages in mammalian hosts and enhanced viral transmission (75, 76).

(SNIP)

The findings from this study have significant implications, even though there are limitations such as small sample sizes and the lack of assessment of transmission from inoculated mammary glands to uninoculated glands from the environment.

However, all experimental studies in dairy cows revealed the restriction of infections and virus replication to infected quarters only. Our experimental approach has demonstrated that small ruminants are susceptible to H5N1 infections. 

The detection of seropositive goats and sheep during periods of heightened H5N1 activity underscores the necessity for more extensive investigations within the small ruminant herds. Once mammary infections with H5N1 have occurred in some lactating ruminants, virus can spread between the udders of lactating ruminants during suckling as some neonates could access milk from cohoused multiple lactating mothers.

This scenario suggests potential for widespread virus transmission within the flocks. We suggest increased surveillance and the implementation of biosecurity measures, especially in mixed-species livestock systems or where large numbers of lactating ruminants and their neonates were cohoused or allowed to graze on communal pastures. 
Moreover, similar to infected dairy cows, milk obtained from infected lactating small ruminants was found to harbor higher levels of infectious viruses. This raises important zoonotic considerations in areas where raw milk consumption is common. Furthermore, the handling of infected small ruminants poses risks to human health, highlighting the need for thorough risk assessments to be carried out.

       (Continue . . . )

Whether sheep, goats, or other small ruminants will ultimately increase the risk of HPAI remains unknowable, but it does give the virus more places where it can hide, thrive, and potentially make genetic improvements. 

Mixed-species farms are particularly worrisome, as they provide novel viruses with access to numerous hosts, and fresh opportunities to reassort or adapt (see Study: Seroconversion of a Swine Herd in a Free-Range Rural Multi-Species Farm against HPAI H5N1 2.3.4.4b Clade Virus).

While the evidence of HPAI H5's growing host range continues to mount, the $64 question remains; can we adapt to the threat faster than the threat is adapting to us?

Stay tuned. 

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