Research

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12 pages, 4319 KiB

Open AccessArticle

Abundant Intra-Subtype Reassortment Revealed in H13N8 Influenza Viruses

by Sofia Feoktistova, Marya Sayganova, Kseniya Trutneva, Olga Glazova, Artem S. Blagodatski, Liudmila Shevkova, Anna Navoikova, Yuriy Anisimov, Eugene Albert, Olga Mityaeva, Pavel Volchkov and Andrey Deviatkin

Viruses 2024, 16(4), 568; https://doi.org/10.3390/v16040568 - 07 Apr 2024

Viewed by 675

Abstract

Influenza A viruses (IAVs) pose a serious threat to global health. On the one hand, these viruses cause seasonal flu outbreaks in humans. On the other hand, they are a zoonotic infection that has the potential to cause a pandemic. The most important [...] Read more.

Influenza A viruses (IAVs) pose a serious threat to global health. On the one hand, these viruses cause seasonal flu outbreaks in humans. On the other hand, they are a zoonotic infection that has the potential to cause a pandemic. The most important natural reservoir of IAVs are waterfowl. In this study, we investigated the occurrence of IAV in birds in the Republic of Buryatia (region in Russia). In 2020, a total of 3018 fecal samples were collected from wild migratory birds near Lake Baikal. Of these samples, 11 were found to be positive for the H13N8 subtype and whole-genome sequencing was performed on them. All samples contained the same virus with the designation A/Unknown/Buryatia/Arangatui-1/2020. To our knowledge, virus A/Unknown/Buryatia/Arangatui-1/2020 is the first representative of the H13N8 subtype collected on the territory of Russia, the sequence of which is available in the GenBank database. An analysis of reassortments based on the genome sequences of other known viruses has shown that A/Unknown/Buryatia/Arangatui-1/2020 arose as a result of reassortment. In addition, a reassortment most likely occurred several decades ago between the ancestors of the viruses recently collected in China, the Netherlands, the United States and Chile. The presence of such reassortment emphasizes the ongoing evolution of the H13N8 viruses distributed in Europe, North and East Asia, North and South America and Australia. This study underscores the importance of the continued surveillance and research of less-studied influenza subtypes. Full article

(This article belongs to the Special Issue Influenza Virus Pathogenesis and Transmission)

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11 pages, 2189 KiB

Open AccessArticle

Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice

by Siqi Tang, Bing Han, Chaofan Su, Hailing Li, Shiyuchen Zhao, Haoyu Leng, Yali Feng and Ying Zhang

Viruses 2024, 16(3), 357; https://doi.org/10.3390/v16030357 - 25 Feb 2024

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Abstract

The H6 subtype of avian influenza viruses (AIVs) has emerged as one of the predominant subtypes in both wild and domestic avian species. Currently, H6 AIVs have acquired the ability to infect a wide range of mammals, though the related molecular mechanisms have [...] Read more.

The H6 subtype of avian influenza viruses (AIVs) has emerged as one of the predominant subtypes in both wild and domestic avian species. Currently, H6 AIVs have acquired the ability to infect a wide range of mammals, though the related molecular mechanisms have yet to be fully investigated. In this study, a wild bird-origin H6N2 AIV was isolated from the East Asian–Australasian migratory flyway region located in Liaoning Province. This H6N2 virus initially expressed limited replication in mice. However, after one passage in mice, the virus acquired two mutations, PB2 E627K and HA A110V. The mutant displayed enhanced replication both in vitro and in vivo, proving lethal to mice. But the mutant retained the α-2, 3-linked sialic acid binding property and failed to transmit in guinea pigs. We explored the molecular mechanisms underlying the pathogenicity difference between the wild type and the mutant. Our findings revealed that PB2 E627K dramatically enhanced the polymerase activity of the H6N2 virus, while the HA A110V mutation decreased the pH of HA activation. This study demonstrated that the H6N2 subtype wild bird-origin AIV easily acquired the mammalian adaptation. The monitoring and evaluation of H6 wild bird-origin AIV should be strengthened. Full article

(This article belongs to the Special Issue Influenza Virus Pathogenesis and Transmission)

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14 pages, 3896 KiB

Open AccessArticle

Cross-Species Transmission Potential of H4 Avian Influenza Viruses in China: Epidemiological and Evolutionary Study

by Shuxia Lin, Ye Zhang, Jiaying Yang, Lei Yang, Xiyan Li, Hong Bo, Jia Liu, Min Tan, Wenfei Zhu, Dayan Wang and Yuelong Shu

Viruses 2024, 16(3), 353; https://doi.org/10.3390/v16030353 - 24 Feb 2024

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Abstract

H4 avian influenza viruses (AIVs) have been widely detected in live poultry markets in China. However, the potential public health impact of H4 AIVs remains largely uncertain. Here, we fully analyzed the distribution and phylogenetic relationship of H4 AIVs in China. We obtained [...] Read more.

H4 avian influenza viruses (AIVs) have been widely detected in live poultry markets in China. However, the potential public health impact of H4 AIVs remains largely uncertain. Here, we fully analyzed the distribution and phylogenetic relationship of H4 AIVs in China. We obtained 31 isolates of H4 viruses in China during 2009–2022 through surveillance in poultry-associated environments, such as live poultry markets and poultry farms. Genomic sequence analysis together with publicly available data revealed that frequent reassortment and introduction of H4 AIV from wild birds to poultry may have occurred. We identified 62 genotypes among 127 whole genome sequences of H4 viruses in China, indicating that H4 AIVs had great genetic diversity in China. We also investigated molecular markers and found that drug resistance mutations frequently occurred in the M2 protein and a few mutations related to receptor binding and the host signature in H4 AIVs. Our study demonstrates the cross-species transmission potential of H4 AIVs in China and provides some reference significance for its risk assessment. Full article

(This article belongs to the Special Issue Influenza Virus Pathogenesis and Transmission)

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12 pages, 2037 KiB

Open AccessArticle

Evolutionary Events Promoted Polymerase Activity of H13N8 Avian Influenza Virus

by Bo Meng, Qian Wang, Haoyu Leng, Chenyang Ren, Chong Feng, Weiwei Guo, Yali Feng and Ying Zhang

Viruses 2024, 16(3), 329; https://doi.org/10.3390/v16030329 - 21 Feb 2024

Cited by 1 | Viewed by 814

Abstract

Wild birds are considered to be the natural reservoir hosts of avian influenza viruses (AIVs). Wild bird-origin AIVs may spill over into new hosts and overcome species barriers after evolutionary adaptation. H13N8 AIVs used to be considered primarily circulated in multispecies gulls but [...] Read more.

Wild birds are considered to be the natural reservoir hosts of avian influenza viruses (AIVs). Wild bird-origin AIVs may spill over into new hosts and overcome species barriers after evolutionary adaptation. H13N8 AIVs used to be considered primarily circulated in multispecies gulls but have recently been shown to possess cross-species infectivity. In this study, we analyzed the genetic changes that occurred in the process of the evolution of H13 AIVs. Phylogenetic analysis revealed that H13 AIVs underwent complex reassortment events. Based on the full genomic diversity, we divided H13 AIVs into 81 genotypes. Reassortment experiments indicated that basic polymerase 2 (PB2) and nucleoprotein (NP) genes of the H9N2 AIV significantly enhanced the polymerase activity of the H13N8 AIV. Using the replication-incompetent virus screening system, we identified two mutations, PB2-I76T and PB2-I559T, which could enhance the polymerase activity of the H13N8 AIV in mammalian cells. Notably, these mutations had been acquired by circulating H13N8 AIVs in 2015. These findings suggest that H13N8 AIVs are about to cross the host barrier. Occasional genetic reassortments with other AIVs and natural mutation events could promote this process. It is imperative to intensify monitoring efforts for H13N8 AIVs. Full article

(This article belongs to the Special Issue Influenza Virus Pathogenesis and Transmission)

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21 pages, 4495 KiB

Open AccessArticle

Genomic Analysis of Influenza A and B Viruses Carrying Baloxavir Resistance-Associated Substitutions Serially Passaged in Human Epithelial Cells

by Brady T. Hickerson, Bruce K. Huang, Svetlana N. Petrovskaya and Natalia A. Ilyushina

Viruses 2023, 15(12), 2446; https://doi.org/10.3390/v15122446 - 16 Dec 2023

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Abstract

Baloxavir marboxil (baloxavir) is an FDA-approved inhibitor of the influenza virus polymerase acidic (PA) protein. Here, we used next-generation sequencing to compare the genomic mutational profiles of IAV H1N1 and H3N2, and IBV wild type (WT) and mutants (MUT) viruses carrying baloxavir resistance-associated [...] Read more.

Baloxavir marboxil (baloxavir) is an FDA-approved inhibitor of the influenza virus polymerase acidic (PA) protein. Here, we used next-generation sequencing to compare the genomic mutational profiles of IAV H1N1 and H3N2, and IBV wild type (WT) and mutants (MUT) viruses carrying baloxavir resistance-associated substitutions (H1N1—PA I38L, I38T, and E199D; H3N2—PA I38T; and IBV—PA I38T) during passaging in normal human bronchial epithelial (NHBE) cells. We determined the ratio of nonsynonymous to synonymous nucleotide mutations (d_N/d_S) and identified the location and type of amino acid (AA) substitutions that occurred at a frequency of ≥30%. We observed that IAV H1N1 WT and MUT viruses remained relatively stable during passaging. While the mutational profiles for IAV H1N1 I38L, I38T, and E199D, and IBV I38T MUTs were relatively similar after each passage compared to the respective WTs, the mutational profile of the IAV H3N2 I38T MUT was significantly different for most genes compared to H3N2 WT. Our work provides insight into how baloxavir resistance-associated substitutions may impact influenza virus evolution in natural settings. Further characterization of the potentially adaptive mutations identified in this study is needed. Full article

(This article belongs to the Special Issue Influenza Virus Pathogenesis and Transmission)

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13 pages, 2956 KiB

Open AccessArticle

Key Amino Acid Residues That Determine the Antigenic Properties of Highly Pathogenic H5 Influenza Viruses Bearing the Clade 2.3.4.4 Hemagglutinin Gene

by Yuancheng Zhang, Pengfei Cui, Jianzhong Shi, Yuan Chen, Xianying Zeng, Yongping Jiang, Guobin Tian, Chengjun Li, Hualan Chen, Huihui Kong and Guohua Deng

Viruses 2023, 15(11), 2249; https://doi.org/10.3390/v15112249 - 13 Nov 2023

Viewed by 1352

Abstract

The H5 subtype highly pathogenic avian influenza viruses bearing the clade 2.3.4.4 HA gene have been pervasive among domestic poultry and wild birds worldwide since 2014, presenting substantial risks to human and animal health. Continued circulation of clade 2.3.4.4 viruses has resulted in [...] Read more.

The H5 subtype highly pathogenic avian influenza viruses bearing the clade 2.3.4.4 HA gene have been pervasive among domestic poultry and wild birds worldwide since 2014, presenting substantial risks to human and animal health. Continued circulation of clade 2.3.4.4 viruses has resulted in the emergence of eight subclades (2.3.4.4a–h) and multiple distinct antigenic groups. However, the key antigenic substitutions responsible for the antigenic change of these viruses remain unknown. In this study, we analyzed the HA gene sequences of 5713 clade 2.3.4.4 viruses obtained from a public database and found that 23 amino acid residues were highly variable among these strains. We then generated a series of single-amino-acid mutants based on the H5-Re8 (a vaccine seed virus) background and tested their reactivity with a panel of eight monoclonal antibodies (mAbs). Six mutants bearing amino acid substitutions at positions 120, 126, 141, 156, 185, or 189 (H5 numbering) led to reduced or lost reactivity to these mAbs. Further antigenic cartography analysis revealed that the amino acid residues at positions 126, 156, and 189 acted as immunodominant epitopes of H5 viruses. Collectively, our findings offer valuable guidance for the surveillance and early detection of emerging antigenic variants. Full article

(This article belongs to the Special Issue Influenza Virus Pathogenesis and Transmission)

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Review

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15 pages, 1464 KiB

Open AccessReview

Existing Evidence for Influenza B Virus Adaptations to Drive Replication in Humans as the Primary Host

by Matthew J. Pekarek and Eric A. Weaver

Viruses 2023, 15(10), 2032; https://doi.org/10.3390/v15102032 - 30 Sep 2023

Cited by 1 | Viewed by 1155

Abstract

Influenza B virus (IBV) is one of the two major types of influenza viruses that circulate each year. Unlike influenza A viruses, IBV does not harbor pandemic potential due to its lack of historical circulation in non-human hosts. Many studies and reviews have [...] Read more.

Influenza B virus (IBV) is one of the two major types of influenza viruses that circulate each year. Unlike influenza A viruses, IBV does not harbor pandemic potential due to its lack of historical circulation in non-human hosts. Many studies and reviews have highlighted important factors for host determination of influenza A viruses. However, much less is known about the factors driving IBV replication in humans. We hypothesize that similar factors influence the host restriction of IBV. Here, we compile and review the current understanding of host factors crucial for the various stages of the IBV viral replication cycle. While we discovered the research in this area of IBV is limited, we review known host factors that may indicate possible host restriction of IBV to humans. These factors include the IBV hemagglutinin (HA) protein, host nuclear factors, and viral immune evasion proteins. Our review frames the current understanding of IBV adaptations to replication in humans. However, this review is limited by the amount of research previously completed on IBV host determinants and would benefit from additional future research in this area. Full article

(This article belongs to the Special Issue Influenza Virus Pathogenesis and Transmission)

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24 pages, 391 KiB

Open AccessReview

Fitness Determinants of Influenza A Viruses

by Emily Fate Griffin and Stephen Mark Tompkins

Viruses 2023, 15(9), 1959; https://doi.org/10.3390/v15091959 - 20 Sep 2023

Cited by 3 | Viewed by 1628

Abstract

Influenza A (IAV) is a major human respiratory pathogen that causes illness, hospitalizations, and mortality annually worldwide. IAV is also a zoonotic pathogen with a multitude of hosts, allowing for interspecies transmission, reassortment events, and the emergence of novel pandemics, as was seen [...] Read more.

Influenza A (IAV) is a major human respiratory pathogen that causes illness, hospitalizations, and mortality annually worldwide. IAV is also a zoonotic pathogen with a multitude of hosts, allowing for interspecies transmission, reassortment events, and the emergence of novel pandemics, as was seen in 2009 with the emergence of a swine-origin H1N1 (pdmH1N1) virus into humans, causing the first influenza pandemic of the 21st century. While the 2009 pandemic was considered to have high morbidity and low mortality, studies have linked the pdmH1N1 virus and its gene segments to increased disease in humans and animal models. Genetic components of the pdmH1N1 virus currently circulate in the swine population, reassorting with endemic swine viruses that co-circulate and occasionally spillover into humans. This is evidenced by the regular detection of variant swine IAVs in humans associated with state fairs and other intersections of humans and swine. Defining genetic changes that support species adaptation, virulence, and cross-species transmission, as well as mutations that enhance or attenuate these features, will improve our understanding of influenza biology. It aids in surveillance and virus risk assessment and guides the establishment of counter measures for emerging viruses. Here, we review the current understanding of the determinants of specific IAV phenotypes, focusing on the fitness, transmission, and virulence determinants that have been identified in swine IAVs and/or in relation to the 2009 pdmH1N1 virus. Full article

(This article belongs to the Special Issue Influenza Virus Pathogenesis and Transmission)

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