Flu Virus binding to Receptor Cells – Credit CDC
#17,983
The CDC this evening has released their analysis of the HPAI H5N1 virus sampled from the human case in Texas, and reports that it is largely similar to HPAI viruses collected from dairy cattle in Texas.
Avian influenza in birds is predominantly a gastrointestinal malady, and is spread mostly via infected droppings. Birds run `hotter’ than mammals, which means avian flu viruses must adapt to lower temperatures found in the respiratory tract if they are to succeed in human or mammalian hosts.They do, however, report finding one well known `mammalian' mutation in the human sample; PB2-E627K.
PB2-E627K describes the swapping out of Glutamic acid (E) for Lysine (K) at position 627 in the PB2 protein, which allows the virus to replicate at lower temperatures found in the human respiratory tract.
Additional adaptations are needed to make an avian virus a genuine pandemic threat (some we know about, while others we may not), but PB2-E627K is an important one often look for.
I've reproduced the CDC's summary and some excerpts. Follow the link to read the full technical report.
Technical Update: Summary Analysis of Genetic Sequences of Highly Pathogenic Avian Influenza A(H5N1) Viruses in Texas
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This is a technical summary of an analysis of the genomic sequences of viruses associated with an outbreak of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Texas. This analysis supports the conclusion that the overall risk to the general public associated with the ongoing HPAI A(H5N1) outbreak has not changed and remains low at this time. The genome of the virus identified from the patient in Texas is publicly posted in GISAID and has been submitted to GenBank.
April 2, 2024 – CDC has sequenced the influenza virus genome identified in a specimen collected from the patient in Texas who was confirmed to be infected with highly pathogenic avian influenza A(H5N1) [“HPAI A(H5N1)”] virus and compared these with HPAI A(H5N1) sequences from cattle, wild birds and poultry. The virus sequences are HA clade 2.3.4.4b HPAI A(H5N1) with each individual gene segment closely related to viruses detected in dairy cattle available from USDA testing in Texas.
While minor changes were identified in the virus sequence from the patient specimen compared to the viral sequences from cattle, both cattle and human sequences maintain primarily avian genetic characteristics and for the most part lack changes that would make them better adapted to infect mammals. The genome for the human isolate had one change (PB2 E627K) that is known to be associated with viral adaptation to mammalian hosts, and which has been detected before in people and other mammals infected with HPAI A(H5N1) virus and other avian influenza subtypes (e.g., H7N9), but with no evidence of onward spread among people.
Viruses can undergo changes in a host as they replicate after infection. Further, there are no markers known to be associated with influenza antiviral resistance found in the virus sequences from the patient’s specimen and the virus is very closely related to two existing HPAI A(H5N1) candidate vaccine viruses that are already available to manufacturers, and which could be used to make vaccine if needed. Overall, the genetic analysis of HPAI A(H5N1) viruses in Texas supports CDC’s conclusion that the human health risk currently remains low. More details are available in this technical summary below:
(SNIP)
The virus sequence was confirmed to be HA clade 2.3.4.4b HPAI A(H5N1) with each individual gene segment determined to be closely related to viruses detected in dairy cattle in Texas. The genotype was classified as B3.13 (1) and corresponds to the same genotype described by USDA for the virus detected in Texas cattle (2). This genotype contains PA, HA, NA and M gene segments from Eurasian wild bird lineages and PB2, PB1, NP and NS gene segments from American wild bird lineages. Other viruses with this genotype have been sporadically detected in wild birds, poultry and one skunk since November 2023 in the U.S. CDC’s real-time RT-PCR diagnostic test used for the detection of A(H5) virus in human samples has not been impacted by genetic changes in B3.13 genotype viruses
(SNIP)
Analysis of the other gene segments (PB2, PB1, PA, NP, M, NS) was also conducted. No known or suspected markers of reduced susceptibility to antiviral compounds that target the PA (i.e., baloxavir marboxil) or M2 (i.e., amantadine, rimantadine) were found.
In addition to the HA and NA, the RNA transcription and replication complex (PB2, PB1, PA, NP) also have species-specific determinants that impact efficient replication in humans and other mammals, particularly polymerase basic protein 2 (PB2). The PB1, PA and NP lacked markers of mammalian adaptation. The PB2 of the human specimen had a change of PB2 E627K compared to the PB2 genes of viruses available from USDA detections in Texas dairy cattle and typically found in A(H5N1) viruses circulating in wild birds. This mutation is, however, commonly found in humans and other mammals that are infected with HPAI A(H5N1) viruses and is understood to be associated with mammalian adaptation because it improves RNA polymerase activity and replication efficiency in mammalian cells; based on experimental studies in mice, guinea pigs and ferrets, it has the potential to impact pathogenesis or transmission in infected mammals (7-8).
Despite previous identification of PB2 E627K in human cases of HPAI A(H5N1) virus, there is no evidence of onward transmission among humans after infection with viruses containing this mutation. It is important to note that this substitution has not been seen in available PB2 genes from viruses circulating in wild birds and poultry or in the recently described cattle viruses detected in Texas, suggesting the mutation may have been acquired in the patient during the development of conjunctivitis. Viruses can undergo changes in a host as they replicate after infection, and it is not uncommon or surprising for HPAI A(H5N1) viruses to undergo this and other polymerase gene changes in infected patients (9). Additional data from A(H5N1) virus-infected animals from the premises where the person was likely exposed is needed to support this hypothesis.
The protein products from the M (M1 and M2) and NS (N1 and N2) genes lacked markers associated with mammalian adaptation. Collectively, epidemiologic, and viral genomic analyses indicate that this case represents a single zoonotic event and while the HA lacked changes likely to enhance transmission to mammals, it did acquire substitutions in PB2 likely to enhance replication in mammals, which illustrates that we have to remain vigilant and continue to characterize zoonotic viruses.
Overall, the genomic analysis of the virus from this human case does not change CDC’s risk assessment related to the HPAI A(H5) clade 2.3.4.4b viruses. The overall risk to human health associated with the ongoing HPAI A(H5) outbreaks in poultry and detections in wild birds and cattle remains low.
