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BOVINE H5N1 INFLUENZA FROM INFECTED WORKER TRANSMISSIBLE AND LETHAL IN ANIMAL
MODELS


SOME ANTIVIRAL DRUGS HIGHLY EFFECTIVE AGAINST BOVINE H5N1

October 28, 2024

Colorized transmission electron micrograph of avian influenza A H5N1 virus
particles (teal) grown in Madin-Darby Canine Kidney (MDCK) epithelial cells.
Microscopy by CDC; repositioned and recolored by NIAID.

Credit: CDC and NIAID

A highly pathogenic avian influenza (HPAI) H5N1 virus, isolated from the eye of
a farm worker who became infected through contact with dairy cows, was lethal in
mice and ferrets infected in a high-containment laboratory environment,
according to a new study in Nature. The study investigators also found that the
virus isolated from the worker, who experienced mild inflammation of the cornea
(conjunctivitis), could be transmitted through the air between separated ferrets
and might be capable of binding to and replicating in human respiratory tract
cells.

The virus isolated from the worker is called huTX37-H5N1 and has a mutation
(PB2-E627K) frequently seen in avian influenza viruses that replicate in
mammals, typically making virus replication more efficient. These mutations
underscore the need for continued monitoring and evaluation of viruses from the
current H5N1 outbreak.

The study also showed that a bovine H5N1 virus is susceptible to the antiviral
drugs favipiravir and baloxavir marboxil (brand name Xofluza) of the polymerase
inhibitor class, as well as the neuraminidase inhibitor zanamivir. The virus is
less sensitive to oseltamivir (Tamiflu), another neuraminidase inhibitor.

In laboratory experiments, huTX37-H5N1 replicated in human cornea and lung
cells. The scientists determined the lethal dose of huTX37-H5N1 as less than 1
plaque-forming unit (PFU) in mice, compared to 31.6 PFU as the lethal dose of a
bovine H5N1 virus isolated from the milk of a lactating cow. The huTX37-H5N1
virus also infected each of 15 different mouse tissues tested, with the highest
virus levels found in respiratory tissues.

Researchers also infected ferrets with a high dose of huTX37-H5N1. Flu
infections in ferrets more closely resemble human flu infections than those in
mice. All infected ferrets died within 5 days and scientists found huTX37-H5N1
virus in all the tissues sampled, with high levels in the respiratory system. In
a prior study, the researchers had infected ferrets with a bovine H5N1 virus
and, although it caused severe disease, lethality was limited.

To evaluate respiratory transmission, the scientists placed healthy ferrets in
cages about 5 centimeters away from ferrets infected one day earlier with one of
four decreasing doses of huTX37-H5N1. All directly infected ferrets died within
6 days and, depending on the exposure dose, between 17 percent and 33 percent of
the nearby animals became infected via respiratory droplet transmission. These
results indicate that a bovine HPAI H5 virus isolated from an infected person
can transmit among mammals via respiratory droplets, though with limited
efficiency.

The authors note that the person infected with the huTX37-H5N1 virus did not
develop severe illness. In fact, human cases reported from the current outbreak
have mostly experienced conjunctivitis and/or mild respiratory symptoms. The
researchers speculate that eye infection with a low dose of bovine H5N1 virus
might result in localized conjunctivitis without severe disease in humans.
Multiple exposures to seasonal human influenza viruses, they say, might provide
people with low levels of protection against currently circulating HPAI H5N1
viruses—though additional study is needed.

In summary, this study characterizes the huTX37-H5N1 isolate, finding that it
may be capable of replicating in cells of the respiratory tract in humans, that
it is pathogenic in mice and ferrets, and that it is capable of being
transmitted by the respiratory route in ferrets. The authors note that “based in
these observations, every effort should be made to contain HPAI H5N1 outbreaks
in dairy cattle to limit the possibility of further human infections.”

Scientists from the University of Wisconsin at Madison led the research with
collaborators from Shizuoka and Tokyo Universities and the Research Center for
Global Viral Diseases in Japan. The National Institute of Allergy and Infectious
Diseases (NIAID), part of the National Institutes of Health, funded much of the
work through its Centers of Excellence for Influenza Research and Response
program.

ARTICLES: 
C Gu et al. A human isolate of bovine H5N1 is transmissible and lethal in animal
models. Nature DOI: 10.1038/s41586-024-08254-7 (2024).

A Eisfeld et al. Pathogenicity and transmissibility of bovine H5N1 influenza
virus in mice and ferrets. Nature DOI: 10.1038/s41586-024-07766-6 (2024).

WHO: 
Lauren Byrd-Leotis, Ph.D., with the Viral Respiratory Diseases Section of
NIAID’s Division of Microbiology and Infectious Diseases, is available to
discuss the findings.


CONTACT

To schedule interviews, contact:
Ken Pekoc
(301) 402-1663(301) 402-1663
NIAIDNews@niaid.nih.gov


Content last reviewed on October 28, 2024
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