Mary Wilson
Well-known member
worobey
1
1d
Due to length constraints on virological.org 12 posts, we are splitting this report into two parts that should be read as a single report. This is Part 2, containing Findings sections 6 through 9, Concluding remarks, Acknowledgements, and References. For Background, Data, Methods, and Findings sections 1 through 5. See Part 1
Michael Worobey, University of Arizona, Tucson, AZ 85705, USA
Karthik Gangavarapu, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
Jonathan E. Pekar, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA
Jeffrey B. Joy, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
Louise Moncla, University of Pennsylvania, PA 19104, USA
Moritz U. G. Kraemer, Department of Biology & Pandemic Sciences Institute, University of Oxford, Oxford, UK
Gytis Dudas, Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
Daniel Goldhill, Department of Pathobiology and Population Sciences, Royal Veterinary College, London, UK.
Christopher Ruis, VPD Heart & Lung Research Institute, Department of Medicine, University of Cambridge, Cambridge, UK
Lorena Malpica Serrano, University of Arizona, Tucson, AZ 85705, USA
Xiang Ji, Department of Mathematics, Tulane University, New Orleans, LA 70118, USA
Kristian G. Andersen, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
Joel O. Wertheim, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA
Philippe Lemey, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium
Marc A Suchard, Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA 90095, USA
Angela L. Rasmussen, Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3
Meera Chand, UK Health Security Agency, London UK
Natalie Groves, UK Health Security Agency, London UK
Oliver G. Pybus, (1) Department of Pathobiology and Population Sciences, Royal Veterinary College, London, UK (2) Department of Biology & Pandemic Sciences Institute, University of Oxford, Oxford, UK
Thomas P. Peacock, The Pirbright Institute, Woking, UK, GU24 0NF; Department of Infectious Disease, Imperial College London, UK, W2 1PG
Andrew Rambaut, Institute of Ecology and Evolution, University of Edinburgh, Edinburgh, UK
Martha I. Nelson, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20892
6. The original cattle H5N1 virus’s HA was not adapted to a human-like receptor.
https://virological.org/t/prelimina...-virus-outbreak-in-u-s-cattle-part-2-of-2/971
1
1d
Due to length constraints on virological.org 12 posts, we are splitting this report into two parts that should be read as a single report. This is Part 2, containing Findings sections 6 through 9, Concluding remarks, Acknowledgements, and References. For Background, Data, Methods, and Findings sections 1 through 5. See Part 1
Michael Worobey, University of Arizona, Tucson, AZ 85705, USA
Karthik Gangavarapu, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
Jonathan E. Pekar, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA
Jeffrey B. Joy, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
Louise Moncla, University of Pennsylvania, PA 19104, USA
Moritz U. G. Kraemer, Department of Biology & Pandemic Sciences Institute, University of Oxford, Oxford, UK
Gytis Dudas, Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
Daniel Goldhill, Department of Pathobiology and Population Sciences, Royal Veterinary College, London, UK.
Christopher Ruis, VPD Heart & Lung Research Institute, Department of Medicine, University of Cambridge, Cambridge, UK
Lorena Malpica Serrano, University of Arizona, Tucson, AZ 85705, USA
Xiang Ji, Department of Mathematics, Tulane University, New Orleans, LA 70118, USA
Kristian G. Andersen, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
Joel O. Wertheim, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA
Philippe Lemey, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium
Marc A Suchard, Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA 90095, USA
Angela L. Rasmussen, Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3
Meera Chand, UK Health Security Agency, London UK
Natalie Groves, UK Health Security Agency, London UK
Oliver G. Pybus, (1) Department of Pathobiology and Population Sciences, Royal Veterinary College, London, UK (2) Department of Biology & Pandemic Sciences Institute, University of Oxford, Oxford, UK
Thomas P. Peacock, The Pirbright Institute, Woking, UK, GU24 0NF; Department of Infectious Disease, Imperial College London, UK, W2 1PG
Andrew Rambaut, Institute of Ecology and Evolution, University of Edinburgh, Edinburgh, UK
Martha I. Nelson, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20892
6. The original cattle H5N1 virus’s HA was not adapted to a human-like receptor.
- In the hemagglutinin (HA), the protein that must bind to the host’s cell-surface sialic acid residues for the virus to gain entry to the host cell, the closest-related sequences to the cattle H5N1 HAs come from wild birds (a Canada goose and a peregrine falcon.) There are no amino acid differences between the HAs of these wild bird sequences and the earliest sequences from cattle.
- This suggests that the first cattle sequences possessed no (pre)adaptation to mammalian cell-surface receptors. Non-synonymous changes in HA have been acquired by small clades of sequences from cattle and cats nested within the cattle clade (n<=11); however, the significance of these mutations is not well understood. Although mutations have been seen in the polymerase of viruses from cattle, similar mutations have been seen in avian viruses infecting humans and other mammals without leading to sustained transmission. Without changes in HA affecting receptor binding, the risk of the virus becoming transmissible between humans is low. The lack of HA changes may also suggest (at least with the current tissue tropism) that there is not strong selective pressure to change receptor binding, suggesting ‘avian-like’ α-2,3-linked sialic acids are abundant in the main sites of replication in these animals. However, this is also true for dogs and pigs, which in the short term do not strongly select for such changes, yet in the longer term, avian-origin H1N1 and H3N2 viruses in these species gradually adapt to ‘human-like’ α-2,6-linked sialic acids(37) 1(38) 1
- Several sequences from wild birds (e.g., blackbird, grackle), poultry, domestic cats, and other wildlife (e.g., raccoon) are nested within the main cattle clade of sequences across each genome segment (Figures 2 & 3; see Figure 7 for concatenated genome tree). This tree topology suggests that the virus may be spilling back from cows into other host species, which is consistent with prior reports of virus transmission between cattle and poultry at individual farms(39, 40)[https://www.doi.org/10.1126/science.zoo2sbi 2]and from cows into cats (15) 1 .
- While most “spillbacks” from cattle were observed in Texas, one cattle-to-poultry transmission was observed in Michigan (clustering with Michigan cattle viruses), and another spillback to raccoons occurred in New Mexico (clustering with New Mexico cattle viruses).
- Whether any onward cat-to-cat or poultry-to-poultry transmission occurred following these spillbacks is difficult to resolve at this time. But these data suggest that H5N1 transmission in cattle is extensive enough to initiate outbreaks in other host species.
- Further evidence of spillback from cattle to other species comes from amino acid changes that are fixed in cattle that are also seen in these birds and other mammals, including two putative mammalian adaptations PB2 M631L and PA K497R. Assuming a single spillover from wild birds into cows, the viruses have likely spread locally from cows back into wild birds, which associate with cattle on farms.
- There have been at least two independent spillbacks to domestic (presumably barn) cats in Texas, most likely due to the consumption of raw milk from infected dairy cattle. H5N1 is known to be highly pathogenic in cats, and early on, dead cats served as sentinels on dairy farms when the symptoms in cattle were less severe and less HPAI-specific (41) 1.
https://virological.org/t/prelimina...-virus-outbreak-in-u-s-cattle-part-2-of-2/971
