Synergistic effects of PA (S184N) and #PB2 (E627K) #mutations on the increased pathogenicity of #H3N2 canine #influenza virus #infections in mice and #dogs

ABSTRACT

As companion animals, dogs are susceptible to various subtypes of influenza A virus (IAV), with the H3N2 and H3N8 subtypes of canine influenza virus (CIV) stably circulating among canines. Compared to the H3N8 CIV, the H3N2 CIV is more widely prevalent in canine populations and demonstrates increased adaptability to mammals, potentially facilitating cross-species transmission. Therefore, a comprehensive elucidation of the mechanisms underlying H3N2 CIV adaptation to mammals is imperative. In this study, we serially passaged the GD14-WT strain in murine lungs, successfully establishing a lethal H3N2 CIV infection model. From this model, we isolated the lethal strain GD14-MA and identified the key lethal mutations PA(S184N) and PB2(E627K). Moreover, the GD14-ma[PA(S184N)+PB2(E627K)] strain exhibited markedly enhanced pathogenicity in dogs. Viral titers in lung tissues from infected dogs and mice showed that GD14-ma[PA(S184N)+PB2(E627K)] does not increase its pathogenicity to mice and dogs by upregulating viral titers compared to the GD14-WT strain. Notably, sequence alignments across all H3N2 IAVs showed an increasing prevalence of the PA (S184N) and PB2 (E627K) mutations from avian to human hosts. Finally, single-cell RNA sequencing of infected mouse lung tissues showed that GD14-ma[PA(S184N)+PB2(E627K)] effectively evaded host antiviral responses, inducing a robust inflammatory reaction. Considering the recognized role of the PB2 (E627K) mutation in the mammalian adaptation of IAVs, our findings underscore the importance of ongoing surveillance for the PA (S184N) mutation in H3N2 IAVs.

IMPORTANCE

Since the 21st century, zoonotic viruses have frequently crossed species barriers, posing significant global public health challenges. Dogs are susceptible to various influenza A viruses (IAVs), particularly the H3N2 canine influenza virus (CIV), which has stably circulated and evolved to enhance its adaptability to mammals, including an increased affinity for the human-like SAα2,6-Gal receptor, posing a potential public health threat. Here, we simulated H3N2 CIV adaptation in mice, revealed that the synergistic PA(S184N) and PB2(E627K) mutations augment H3N2 CIV pathogenicity in dogs and mice, and elucidated the underlying mechanisms at the single-cell level. Our study provides molecular evidence for adapting the H3N2 CIV to mammals and underscores the importance of vigilant monitoring of genetic variations in H3N2 CIV.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01984-24?af=R

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#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

{Excerpt} A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments : M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic , expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries . The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat .1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts , including vertical transmissions , neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential .5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in ext...

Stability of #influenza viruses in the #milk of #cows and #sheep

Abstract In late 2023, H5N1 high pathogenicity avian influenza (HPAIV) started circulating in dairy cattle in the USA . High viral titres were detected in milk from infected cows , raising concerns about onwards human infections . Although pasteurisation was shown to effectively inactivate influenza viruses in milk, unpasteurised milk still poses a risk of infection, both from occupational exposure in dairies and from the consumption of raw milk. We therefore assessed how long influenza viruses could remain infectious for in milk without heat inactivation. We examined the stability of a panel of influenza viruses in milk , including a contemporary H5N1 HPAIV and a variety of other influenza A and D viruses. We incubated viruses in cows' milk under laboratory conditions : at room temperature to simulate exposure in dairies and at 4°C to simulate exposure to refrigerated raw milk. Following an isolated report of H5N1 viral RNA being detected in milk from a sheep in the UK , we also c...

#Evidence of #Viremia in Dairy #Cows Naturally Infected with #Influenza A {#H5N1} Virus, #California, #USA

Abstract We confirmed influenza A virus (IAV) by PCR in serum from 18 cows on 3 affected dairy farms in California, USA . Our findings indicate the presence of viremia and might help explain IAV transmission dynamics and shedding patterns in cows. An understanding of those dynamics could enable development of IAV mitigation strategies. Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/7/25-0134_article ____

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