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- Identification of Rare PB2-D701N Mutation from a Patient with Severe … Sequence analysis of the other three human isolates containing PB2-D701N mutation indicated that their HA protein was the human protein present among circulating A … Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus.Lancet 351 472-477. 10.1016/S0140-6736(97)11212- …
- Transmission of Influenza Virus in a Mammalian Host Is Increased by PB2 … Again, sequencing of the PB2 gene of one transmitted virus indicated that both the K627E and D701N mutations were retained. Thus, the amino acid change PB2 D701N favors the transmission of an H5N1 virus in a mammalian host and this mutation fully compensates for the lack of a lysine at position 627 in terms of transmission by the contact route.
- PB2 Mutations D701N and S714R Promote Adaptation of an Influenza H5N1 … Mutation D701N has been observed in the PB2 protein of about 7% of human H5N1 isolates, including strain A/Thailand/1(Kan-1)/04 (Kan-1 virus) .There is also evidence that this mutation contributes to the pathogenicity of H5N1 viruses in mice (19, 22).In the NLS region of PB2 where D701N is located, mutations have also been observed at……known to help the bird-adapted virus replicate in mammals more efficiently (PB2 D701N). To date, this mutation has not been seen in D1.1 strains spreading in wild birds nor has it been seen in the B3.13 genotype circulating in dairy cows. Though, it was seen before in a 2023 human case in Chile. The CDC said it has confirmed that the strain of D1.1 infecting the person in Nevada also contains the PB2 D701N mutation.
- Expert Interview: The PB2-D701N Mutation in Influenza Virus Transmission
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376584/
Transmission of Influenza Virus in a Mammalian Host Is Increased by PB2 … Again, sequencing of the PB2 gene of one transmitted virus indicated that both the K627E and D701N mutations were retained. Thus, the amino acid change PB2 D701N favors the transmission of an H5N1 virus in a mammalian host and this mutation fully compensates for the lack of a lysine at position 627 in terms of transmission by the contact route.
URL: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000252
PB2 Mutations D701N and S714R Promote Adaptation of an Influenza H5N1 … Mutation D701N has been observed in the PB2 protein of about 7% of human H5N1 isolates, including strain A/Thailand/1(Kan-1)/04 (Kan-1 virus) .There is also evidence that this mutation contributes to the pathogenicity of H5N1 viruses in mice (19, 22).In the NLS region of PB2 where D701N is located, mutations have also been observed at……known to help the bird-adapted virus replicate in mammals more efficiently (PB2 D701N). To date, this mutation has not been seen in D1.1 strains spreading in wild birds nor has it been seen in the B3.13 genotype circulating in dairy cows. Though, it was seen before in a 2023 human case in Chile. The CDC said it has confirmed that the strain of D1.1 infecting the person in Nevada also contains the PB2 D701N mutation.
The USDA and CDC both reported that no other concerning mutations were found, including one that has been consistently identified in the B3.13 strain in cows. The CDC said it does not expect any changes to how the virus will interact with human immune responses or to antivirals.
Most importantly, to date, there has been no evidence of human-to-human transmission, which would mark a perilous turn for the virus’s ability to spark an outbreak. For all these reasons, the CDC considers the risk to the public low, though people with exposure to poultry, dairy cows, and birds are at higher risk and should take precautions.
To date, 967 herds across 16 states have been infected with H5N1 bird flu, and nearly 158 million commercial birds have been affected since 2022.
Expert Interview: The PB2-D701N Mutation in Influenza Virus Transmission
In the face of ongoing concerns about avian influenza, especially the H5N1 strain, scientists are investigating specific mutations that may impact viral transmission and pathogenicity. One mutation, PB2-D701N, has gained significant attention. in this interview, Dr. Emily Hart, a leading virologist and influenza expert, discusses the implications of this mutation with Senior Editor John Thompson from World Today News.
Introduction to PB2-D701N mutation
John Thompson (JT): Dr. Hart, can you start by explaining what the PB2-D701N mutation is and why it is significant in the context of influenza viruses?
Dr.Emily Hart (EH): Certainly, John.The PB2-D701N mutation refers to a specific change in the PB2 protein of the influenza virus, where the amino acid aspartic acid (D) is replaced by asparagine (N) at position 701. This mutation is significant because it has been observed to enhance the virus’s ability to transmit among mammals. Initial studies demonstrated that this change helps the influenza virus adapt to its mammalian host, facilitating easier spread between hosts.
Transmission Enhancement in Mammalian Hosts
JT: How does the PB2-D701N mutation influence the transmission of the influenza virus in mammals?
EH: Research indicates that the PB2-D701N mutation enhances the transmission of H5N1 viruses in mammalian hosts. It effectively compensates for the lack of another crucial mutation, K627E, in terms of transmission.This means that even without the lysine at position 627,the virus can still transmit efficiently,making it a notable adaptation for mammalian hosts.
Pathogenicity and Adaptive Mechanisms
JT: How does this mutation relate to the pathogenicity of influenza viruses, especially in human cases?
EH: The PB2-D701N mutation has been observed in approximately 7% of human H5N1 isolates and is known to contribute to the virus’s pathogenicity in mice. This mutation occurs in the nuclear localization signal (NLS) region of the PB2 protein, facilitating more efficient replication in mammalian cells. Its presence in the Kan-1 virus strain and recent human cases also underscores its relevance as an adaptive mechanism in human infections.
Recent Findings and Implications
JT: There have been recent reports of the PB2-D701N mutation in human cases, including one in Nevada. What do these findings imply?
EH: The recent revelation of the PB2-D701N mutation in a human case in Nevada is notable for several reasons.Firstly, it underscores the virus’s ongoing adaptation to human hosts.Secondly,while the mutation itself does not appear to alter the virus’s interaction with human immune responses or antivirals,it highlights the need for continued vigilance. Fortunately, there is currently no evidence of human-to-human transmission, even though individuals with poultry exposure remain at higher risk.
Conclusion
JT: What are the main takeaways from our discussion, and what advice would you give to the public regarding avian influenza?
EH: The main takeaway is that the PB2-D701N mutation contributes to the influenza virus’s adaptability and transmissibility in mammalian hosts. While it poses a concern, the lack of human-to-human transmission so far keeps the public risk relatively low. Though, individuals exposed to poultry, dairy cows, and wild birds should take precautions, and the public should remain informed about ongoing developments. Continued surveillance and research are crucial to understanding and mitigating the impact of avian influenza.
over 967 herds across 16 states have been infected with H5N1 bird flu, affecting nearly 158 million commercial birds since 2022.
