#17,956
Almost a year ago Chile's MOH Reported Their 1st Human H5N1 Infection in a 53 year-old man who had no known contact with poultry. He did, however, live very near a beach where many birds had recently died from avian flu.
The patient survived, but was seriously ill and on a ventilator for weeks.
In April of last year the CDC published their Genomic Analysis of H5 Virus In Human in Chile, citing two noteworthy `mammalian adaptations' found in the PB2 gene.
- The PB2-D701N mutation, which has been linked to increased severity of infection (see here and here), and has been previously seen in both human H5N1 and H5N6 infections.
- The PB2-Q591K mutation, which enhances polymerase activity and virus replication of avian viruses in mammals (see PB2-Q591K Mutation Determines the Pathogenicity of Avian H9N2 Influenza Viruses for Mammalian Species).
Since neither of these adaptations had been found in local poultry or wild birds, it was assumed these are most likely host adaptations that occurred after the patient was infected.
While worrisome signs, the impact of these changes can vary, depending upon other factors (i.e. clade, genotype, or other amino acid substitutions in the genome). In order to better quantify their impact, laboratory studies - using ferrets or other lab animals, and human cell lines - are required.
Today we have a study, published in Emerging Microbes & Infections, that does exactly that.
This is a lengthy, and detailed report, but in brief, ferrets infected with this mutated virus developed severe and/or fatal disease, and the virus transmitted well between co-housed ferrets. Additionally, the virus displayed `enhanced replicative ability in human respiratory tract cells'.
There was some `good news', as the virus did not appear to spread efficiently via the airborne route.
The ability to transmit between co-housed ferrets represents an important change in the clade 2.3.4.4b H5N1 virus, but the authors point out that `. . . our results indicate the virus would require further adaptation to mammals to acquire an airborne transmissible phenotype and potentially become a pandemic virus.'
Highly pathogenic avian influenza A(H5N1) virus of clade 2.3.4.4b isolated from a human case in Chile causes fatal disease and transmits between co-housed ferrets.
Joanna A. Pulit-Penaloza, Nicole Brock, Jessica A. Belser, Xiangjie Sun, Claudia Pappas,
Troy J. Kieran, show all
Article: 2332667 | Accepted author version posted online: 17 Mar 2024
https://doi.org/10.1080/22221751.2024.2332667
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Abstract
Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses have caused large outbreaks within avian populations on five continents, with concurrent spillover into a variety of mammalian species. Mutations associated with mammalian adaptation have been sporadically identified in avian isolates, and more frequently among mammalian isolates following infection. Reports of human infection with A(H5N1) viruses following contact with infected wildlife have been reported on multiple continents, highlighting the need for pandemic risk assessment of these viruses.
In this study, the pathogenicity and transmissibility of A/Chile/25945/2023 HPAI A(H5N1) virus, a novel reassortment with four gene segments (PB1, PB2, NP, MP) from North America lineage, isolated from a severe human case in Chile, was evaluated in vitro and using the ferret model. This virus possessed a high capacity to cause fatal disease, characterized by high morbidity and extrapulmonary spread in virus-inoculated ferrets.
The virus was capable of transmission to naïve contacts in a direct contact setting, with contact animals similarly exhibiting severe disease, but did not exhibit productive transmission in respiratory droplet or fomite transmission models.
Our results indicate that the virus would need to acquire an airborne transmissible phenotype in mammals to potentially cause a pandemic. Nonetheless, this work warrants continuous monitoring of mammalian adaptations in avian viruses, especially in strains isolated from humans, to aid pandemic preparedness efforts.
(SNIP)
Analysis of the Chile/25945 A(H5N1) virus sequence revealed that this virus acquired four genes (PB2, PB1, NP, MP) of North American lineages and possessed several mammalian adaptation markers [19]. Two amino acid substitutions found in PB2, Q591K and D701N, have been previously associated with increased polymerase activity in mammalian cell lines and increased virulence in mammalian models [20]. These observations suggested that the reassortant Chile/25945 H5N1 virus may have an increased ability to replicate in mammalian cells and have an increased pathogenicity in the mammalian animal model.
(SNIP)
Discussion
(Excerpt)
Previously analyzed clade 2.3.4.4b A(H5N1) strains were not transmissible between ferrets [16,25]. Here we show that the Chile/25945 A(H5N1) was able to transmit between co-housed ferrets.
Two out of the three contacts tested positive for virus in their nasal washes and tissues, indicating productive transmission. The third contact had no detectable virus in any of the samples collected, but the sera showed evidence of exposure to the challenge virus as seroconversion was observed. When ferrets are co-housed, transmission can occur by direct contact between the infected and naïve ferret, by indirect contact via contaminated fomites (cage walls, bedding, etc.), or by inhalation of virus-laden particles.
As supported by results from our fomite transmission and respiratory droplet transmission experiments, our data suggest that Chile/25945 A(H5N1) virus transmission likely occurred via close, direct ferret-to-ferret contact, rather than through contact with contaminated surfaces or inhalation.
Despite the presence of Chile/25945 A(H5N1) viral RNA in the air, the transmission experiment results show that infectious load of virus in the air was not sufficient for the virus to transmit to ferrets housed in adjacent cages. Measurements of infectious virus in NW (mean maximum titers of 7.5 ±1.1 log10 EID50/ml) as compared to RNA copy titers (mean maximum titers of 9.2 ±0.7 log10 RNA copies/ml) suggest that levels of infectious virus in the air were at least 1.7 orders of magnitude lower than the detected RNA levels, though this remains to be experimentally confirmed.
Despite the logistical challenges associated with this work, our findings support the need for additional efforts to quantify both infectious virus and viral RNA in air samples from inoculated ferrets [29]. Furthermore, studies such as this, which include assessments of multiple transmission modes, improve our understanding the factors contributing to onward transmission of virus.
Collectively, the clade 2.3.4.4b Chile/25945 A(H5N1) virus studied here displayed enhanced replicative ability in human respiratory tract cells and heightened transmissibility between ferrets in comparison to previously tested strains of the same clade isolated from avian and wild mammals [16,25].
However, our results indicate the virus would require further adaptation to mammals to acquire an airborne transmissible phenotype and potentially become a pandemic virus. Nonetheless, this work warrants continuous monitoring of human adaptations in avian viruses, especially in strains isolated from humans, to aid pandemic preparedness efforts.
