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#pathogenicity

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Giuseppe Michieli

#Origin, #pathogenicity, and #transmissibility of a #human isolated #influenza A(#H10N3) virus from #China, Emerg Microbes Infect.: tandfonline.com/doi/full/10.10

Human isolated H10N3 also showed respiratory #droplet #transmissibility in #ferrets. Considering continuous circulation in avian populations and repeated transmission to humans, strengthened #surveillance of H10 subtype viruses in poultry should be put into effect.

Giuseppe Michieli

#SARS-CoV-2 #JN1 reveals attenuated #pathogenicity and #airborne #transmission

Source: BioRxIV, AbstractJN.1 is a subvariant of SARS-CoV-2 Omicron BA.2.86 lineage that was predominant worldwide in early 2024, of which the in vivo characteristics are largely unknown. Our results demonstrated that the replication of JN.1 was more efficient than that of the parental BA.2 in Vero cells, which demonstrated low dependence on TMPRSS2. Compared to Omicron variants BA.2 and XBB…

etidioh.wordpress.com/2024/11/

ETIDIoH · #SARS-CoV-2 #JN1 reveals attenuated #pathogenicity and #airborne #transmission
More from ETIDIoH
Giuseppe Michieli

#Replication #Kinetics, #Pathogenicity and Virus-induced Cellular Responses of #Cattle-origin #Influenza A(#H5N1) Isolates from #Texas, United States

Source: BioRxIV, AbstractThe host range of HPAIV H5N1 was recently expanded to include ruminants, particularly dairy cattle in the United States. Shortly after, human H5N1 infection was reported in a dairy worker in Texas following exposure to infected cattle. Herein, we rescued the cattle-origin influenza…

etidioh.wordpress.com/2024/10/

ETIDIoH · #Replication #Kinetics, #Pathogenicity and Virus-induced Cellular Responses of #Cattle-origin #Influenza A(#H5N1) Isolates from #Texas, United StatesSource: BioRxIV, AbstractThe host range of HPAIV H5N1 was recently expanded to include ruminants, particularly dairy cattle in the United States. Shortly after, human H5N1 infection was reported in…
Giuseppe Michieli

#Lineage-specific #pathogenicity, immune #evasion, and virological #features of #SARS-CoV-2 #BA286 / #JN1 and #EG51 / HK.3

Source: Nature Communications, AbstractSARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared with its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated the immune resistance of SARS-CoV-2 JN.1 but additional factors are speculated to contribute to…

etidioh.wordpress.com/2024/10/

ETIDIoH · #Lineage-specific #pathogenicity, immune #evasion, and virological #features of #SARS-CoV-2 #BA286 / #JN1 and #EG51 / HK.3Source: Nature Communications, AbstractSARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared with its parental variant BA.2.86 has outcompeted all earlier variants to become the …
Giuseppe Michieli

#Hemagglutinin and #neuraminidase of a non-pathogenic #H7N7 avian #influenza virus coevolved during acquisition of intranasal #pathogenicity in #chickens, Arch Virol.: link.springer.com/article/10.1

This study demonstrates that viruses that are highly pathogenic when administered intranasally require additional adaptations for increased pathogenicity to be highly lethal to intranasally infected chickens.

SpringerLinkHemagglutinin and neuraminidase of a non-pathogenic H7N7 avian influenza virus coevolved during the acquisition of intranasal pathogenicity in chickens - Archives of VirologyPolybasic amino acid residues at the hemagglutinin (HA) cleavage site are insufficient to induce the highly pathogenic phenotype of avian influenza viruses in chickens. In our previous study, an H7N7 avian influenza virus named “Vac2sub-P0”, which is nonpathogenic despite carrying polybasic amino acids at the HA cleavage site, was passaged in chick air sacs, and a virus with high intravenous pathogenicity, Vac2sub-P3, was obtained. Intranasal infection with Vac2sub-P3 resulted in limited lethality in chickens; therefore, in this study, this virus was further passaged in chicken lungs, and the resultant virus, Vac2sub-P3L4, acquired high intranasal pathogenicity. Experimental infection of chickens with recombinant viruses demonstrated that mutations in HA and neuraminidase (NA) found in consecutive passages were responsible for the increased pathogenicity. The HA and NA functions of Vac2sub-P3L4 were compared with those of the parental virus in vitro; the virus growth at 40 °C was faster, the binding affinity to a sialic acid receptor was lower, and the rate of release by NA from the cell surface was lower, suggesting that these changes enabled the virus to replicate efficiently in chickens with high intranasal pathogenicity. This study demonstrates that viruses that are highly pathogenic when administered intranasally require additional adaptations for increased pathogenicity to be highly lethal to intranasally infected chickens.
Giuseppe Michieli

#Pathogenicity of HPAI #H5N1 Viruses Isolated from #Cats in Mice & #Ferrets, S #Korea, 2023, Emerg Infect Dis.: wwwnc.cdc.gov/eid/article/30/1

H5N1 clade 2.3.4.4b viruses isolated from 2 cats harbored mutations in the PB2 gene encoding single amino acid substitutions E627K or D701N, which are associated with virus adaptation in mammals. We analyzed pathogenicity & transmission of cat-derived viruses in other mammals. Both isolates caused fatal infections in mice & ferrets.

Emerging Infectious Diseases journalPathogenicity of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Cats in Mice and Ferrets, South Korea, 2023Avian Influenza A(H5N1) Viruses, South Korea, 2023
Giuseppe Michieli

#Molecular basis of #pathogenicity of recently emerged #FCoV23 #coronavirus, BioRxIV: biorxiv.org/content/10.1101/20

FCoV-23 is a recently emerged, highly pathogenic #recombinant coronavirus responsible for a widespread #outbreak of #feline infectious #peritonitis (FIP) likely linked to in-host viral evolution. Here, we report cryoEM structures of two FCoV-23 spike (S) isoforms explaining that the in-host loss of domain 0 observed in clinical samples enhances entry into cells ...

bioRxiv · Molecular basis of pathogenicity of the recently emerged FCoV-23 coronavirusThe ability of coronaviruses to recombine and cross species barriers affects human and animal health globally and is a pandemic threat. FCoV-23 is a recently emerged, highly pathogenic recombinant coronavirus responsible for a widespread outbreak of feline infectious peritonitis (FIP) likely linked to in-host viral evolution. Here, we report cryoEM structures of two FCoV-23 spike (S) isoforms explaining that the in-host loss of domain 0 observed in clinical samples enhances entry into cells and fusogenicity by facilitating protease access, leading to biotype switching and lethality. We show that FCoV-23 can use several aminopeptidase N (APN) orthologs as receptors and reveal the molecular determinants of receptor species tropism, including a glycan modulating human receptor utilization. We define antigenic relationships among alphacoronaviruses infecting humans and other mammalian species and identify a cross-reactive alphacoronavirus monoclonal antibody inhibiting FCoV-23 pseudovirus entry, paving the way for vaccine and therapeutic development targeting this highly pathogenic virus. ### Competing Interest Statement N.P.K. and D.V. are named as inventors on patents for coronavirus nanoparticle vaccines filed by the University of Washington. N.P.K. is a paid consultant of Icosavax, Inc. and has received unrelated sponsored research agreements from Pfizer and GSK. J.D.B. is on the scientific advisory boards of Apriori Bio, Invivyd, and the Vaccine Company. JDB consults for GlaxoSmithKline.
Giuseppe Michieli

Evaluating #epizootic & #zoonotic #threat of an #H7N9 #LPAIV #variant associated with enhanced #pathogenicity in #turkeys. J Gen Virol.: microbiologyresearch.org/conte

H7N9 infection in turkeys can generate novel variants with increased #risk through altered pathogenicity and potential HA antigenic #escape. These findings emphasize the requirement for enhanced #surveillance and understanding of A/Anhui/1/13-lineage viruses and their risk to different species.

microbiologyresearch.orgEvaluating the epizootic and zoonotic threat of an H7N9 low-pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeysBetween 2013 and 2017, the A/Anhui/1/13-lineage (H7N9) low-pathogenicity avian influenza virus (LPAIV) was epizootic in chickens in China, causing mild disease, with 616 fatal human cases. Despite poultry vaccination, H7N9 has not been eradicated. Previously, we demonstrated increased pathogenesis in turkeys infected with H7N9, correlating with the emergence of the L217Q (L226Q H3 numbering) polymorphism in the haemagglutinin (HA) protein. A Q217-containing virus also arose and is now dominant in China following vaccination. We compared infection and transmission of this Q217-containing ‘turkey-adapted’ (ty-ad) isolate alongside the H7N9 (L217) wild-type (wt) virus in different poultry species and investigated the zoonotic potential in the ferret model. Both wt and ty-ad viruses demonstrated similar shedding and transmission in turkeys and chickens. However, the ty-ad virus was significantly more pathogenic than the wt virus in turkeys but not in chickens, causing 100 and 33% mortality in turkeys respectively. Expanded tissue tropism was seen for the ty-ad virus in turkeys but not in chickens, yet the viral cell receptor distribution was broadly similar in the visceral organs of both species. The ty-ad virus required exogenous trypsin for in vitro replication yet had increased replication in primary avian cells. Replication was comparable in mammalian cells, and the ty-ad virus replicated successfully in ferrets. The L217Q polymorphism also affected antigenicity. Therefore, H7N9 infection in turkeys can generate novel variants with increased risk through altered pathogenicity and potential HA antigenic escape. These findings emphasize the requirement for enhanced surveillance and understanding of A/Anhui/1/13-lineage viruses and their risk to different species.
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