TY - JOUR

T1 - Pathobiology of Highly Pathogenic Avian Influenza A (H5N1 Clade 2.3.4.4b) Virus from Pinnipeds on Tyuleniy Island in the Sea of Okhotsk, Russia

AU - Alekseev, Alexander

AU - Sobolev, Ivan

AU - Sharshov, Kirill

AU - Gulyaeva, Marina

AU - Kurskaya, Olga

AU - Kasianov, Nikita

AU - Chistyaeva, Maria

AU - Ivanov, Alexander

AU - Ohlopkova, Olesia

AU - Moshkin, Aleksey

AU - Stepanyuk, Marina

AU - Derko, Anastasiya

AU - Solomatina, Mariya

AU - Mutashev, Batyrgishi

AU - Dolgopolova, Mariya

AU - Gadzhiev, Alimurad

AU - Shestopalov, Alexander

N1 - The study was supported by a Russian Science Foundation grant (Project No. 23-64-00005). The animal work was carried out with the support of the Ministry of Science and Higher Education of the Russian Federation under State Assignment 125031903984-1.

PY - 2026

Y1 - 2026

N2 - Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b has recently emerged as a major threat to wildlife, agriculture, and public health due to its expanding host range and the increasing frequency of spillover into mammals. In July–August 2023, the mass death of over 3500 northern fur seals (Callorhinus ursinus) and at least one Steller sea lion (Eumetopias jubatus) was recorded on Tyuleniy Island in the Sea of Okhotsk, Russia. Two HPAI A(H5N1) viruses were isolated from fur seal carcasses and designated A/Northern_fur_seal/Russia_Tyuleniy/74/2023 and A/Northern_fur_seal/Russia_Tyuleniy/75/2023. Both viruses exhibited high pathogenicity in chickens (IVPI 2.7–3.0) and mice (MLD50 1.9–2.5 log10EID50/mL), with distinct differences in disease progression, histopathology, and organ tropism. Experimental infection of mice revealed that strain A/74/2023 induced more severe pulmonary and neurological lesions than A/75/2023. Whole-genome sequencing and phylogenetic analysis demonstrated close relatedness to HPAI H5N1 strains circulating in the Russian Far East and Japan from 2022 to 2023, with several mutations associated with mammalian adaptation, including NP-N319K and, in one isolate, PB2-E627K. According to our findings, northern fur seals (Callorhinus ursinus) on Tyuleniy Island acted as spillover hosts for the highly pathogenic avian influenza (HPAI) H5N1 virus of clade 2.3.4.4b. Furthermore, the high population density of fur seals and the extensive mortality observed during the outbreak highlight these animals’ potential role as another vessel for the evolution of avian influenza viruses. This study represents the first documented case of HPAI H5N1 in pinnipeds in the North Pacific region and supports previous reports indicating that pinnipeds, including northern fur seals, are highly susceptible to HPAI H5N1 clade 2.3.4.4b viruses.

AB - Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b has recently emerged as a major threat to wildlife, agriculture, and public health due to its expanding host range and the increasing frequency of spillover into mammals. In July–August 2023, the mass death of over 3500 northern fur seals (Callorhinus ursinus) and at least one Steller sea lion (Eumetopias jubatus) was recorded on Tyuleniy Island in the Sea of Okhotsk, Russia. Two HPAI A(H5N1) viruses were isolated from fur seal carcasses and designated A/Northern_fur_seal/Russia_Tyuleniy/74/2023 and A/Northern_fur_seal/Russia_Tyuleniy/75/2023. Both viruses exhibited high pathogenicity in chickens (IVPI 2.7–3.0) and mice (MLD50 1.9–2.5 log10EID50/mL), with distinct differences in disease progression, histopathology, and organ tropism. Experimental infection of mice revealed that strain A/74/2023 induced more severe pulmonary and neurological lesions than A/75/2023. Whole-genome sequencing and phylogenetic analysis demonstrated close relatedness to HPAI H5N1 strains circulating in the Russian Far East and Japan from 2022 to 2023, with several mutations associated with mammalian adaptation, including NP-N319K and, in one isolate, PB2-E627K. According to our findings, northern fur seals (Callorhinus ursinus) on Tyuleniy Island acted as spillover hosts for the highly pathogenic avian influenza (HPAI) H5N1 virus of clade 2.3.4.4b. Furthermore, the high population density of fur seals and the extensive mortality observed during the outbreak highlight these animals’ potential role as another vessel for the evolution of avian influenza viruses. This study represents the first documented case of HPAI H5N1 in pinnipeds in the North Pacific region and supports previous reports indicating that pinnipeds, including northern fur seals, are highly susceptible to HPAI H5N1 clade 2.3.4.4b viruses.

UR - https://www.scopus.com/pages/publications/105028524955

UR - https://www.mendeley.com/catalogue/3e1e5490-5a77-367c-b0bf-e161f61cf677/

U2 - 10.3390/v18010051

DO - 10.3390/v18010051

M3 - Article

C2 - 41600816

VL - 18

JO - Viruses

JF - Viruses

SN - 1999-4915

IS - 1

M1 - 51

ER -