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De Conto, F. Avian Influenza A Viruses Modulate the Cellular Cytoskeleton. Encyclopedia. Available online: (accessed on 17 April 2024).
De Conto F. Avian Influenza A Viruses Modulate the Cellular Cytoskeleton. Encyclopedia. Available at: Accessed April 17, 2024.
De Conto, Flora. "Avian Influenza A Viruses Modulate the Cellular Cytoskeleton" Encyclopedia, (accessed April 17, 2024).
De Conto, F. (2024, March 27). Avian Influenza A Viruses Modulate the Cellular Cytoskeleton. In Encyclopedia.
De Conto, Flora. "Avian Influenza A Viruses Modulate the Cellular Cytoskeleton." Encyclopedia. Web. 27 March, 2024.
Avian Influenza A Viruses Modulate the Cellular Cytoskeleton

Influenza is one of the most prevalent causes of death worldwide. Influenza A viruses (IAVs) naturally infect various avian and mammalian hosts, causing seasonal epidemics and periodic pandemics with high morbidity and mortality. The recent SARS-CoV-2 pandemic showed how an animal virus strain could unpredictably acquire the ability to infect humans with high infection transmissibility. Importantly, highly pathogenic avian influenza A viruses (AIVs) may cause human infections with exceptionally high mortality. Because these latter infections pose a pandemic potential, analyzing the ecology and evolution features of host expansion helps to identify new broad-range therapeutic strategies. Although IAVs are the prototypic example of molecular strategies that capitalize on their coding potential, the outcome of infection depends strictly on the complex interactions between viral and host cell factors. Most of the studies have focused on the influenza virus, while the contribution of host factors remains largely unknown. Therefore, a comprehensive understanding of mammals’ host response to AIV infection is crucial.

avian influenza A virus pandemic zoonosis pathogenicity mammalian adaptation host species barrier cytoskeleton

1. Avian Influenza A Virus Infection Transmission to Humans

AIVs are globally challenging due to widespread circulation. They are differentiated into low- and high-pathogenic viral strains. Low-pathogenic viral strains only cause mild illness in domestic birds. Conversely, highly pathogenic avian phenotypes, such as H5N1, H5N8, and H7N9, may cause organ damage, affect the respiratory tract, and determine up to 100% bird mortality [1][2]. Generally, highly pathogenic AIVs emerge from low-pathogenic viruses, acquiring cleavage site insertions that promote systemic infections [3].
AIVs show the potential to be episodically transmitted from birds to other animals and humans by direct contact or through an intermediate host. AIV infections in humans range in severity from no symptoms or mild illness (fever, conjunctivitis, and mild influenza-like upper respiratory symptoms) to severe diseases (pneumonia, acute respiratory distress syndrome, multi-organ dysfunction, and encephalopathy) and death; less common infection signs include diarrhea, nausea, vomiting, and seizures [4]. Most serious illnesses and high mortality rates have been associated with the Asian lineages H7N9 and H5N1 [5][6].
Although AIVs spread from one infected person to close contacts, prolonged and unprotected contact is rare and generally limited to a few people, there is a global concern that highly pathogenic AIVs (H5/H7/H9/H10) are adapting to other species by acquiring mutations in animals or humans that support their cross-species transmission [7][8][9][10]. Notably, the segmented RNA genome allows IAVs from different species to mix their genes by reassortment, generating new viruses. Important, adaptation processes of AIVs are needed for their efficient transmission and replication in mammal hosts. This aspect first includes the receptor–binding specificity switch of HA to the mammalian sialic acid 2,6 galactose-type receptor [11]. Moreover, the presence of specific mutations in the viral polymerase complex is considered an important host range determinant [12][13]. In addition, the NA of AIVs contains a specific sialic acid-binding site that is absent in human IAV, affecting the catalytic enzyme activity [14].
Since 1996, 11 subtypes of AIVs have been assessed to spread directly from infected birds to humans. Importantly, infected humans can transmit influenza viruses to other animals (pigs, poultry, cats, and dogs). This phenomenon is called reverse zoonosis and may contribute to the further diffusion of influenza viruses [15].
The highly pathogenic H5N1 AIV subtype emerged in China in 1996, establishing sustained transmission in domestic poultry [16]. From 1997, H5N1 human infections occurred in Asian countries with high mortality levels [17][18]; the results of serological assays demonstrated the human-to-human virus spread [19][20]. In a second distribution wave in 2003, the H5N1 virus was disseminated in Asia and Europe through migratory birds [21]. From 2003, several human H5N1 infection episodes were reported worldwide, and, up to 2023, the WHO documented 457 fatalities [22]. Since 2021, the H5N1 virus caused several infections in wild carnivores, mink farms, and marine mammals [23]. The wider range of H5N1 infections and the involvement of different animal species have favored the emergence of new and potentially more virulent variants. Importantly, continuous genetic variability has been observed for the H5N1 virus across various geographic regions as well as increased virulence as it evolves [16][24][25][26][27][28]. In 2014, a fatal human infection by the novel H5N6 AIV was also reported [29].
H9N2 AIV has been circulating in poultry since 1994 and is occasionally transmitted to humans [30][31][32]. Importantly, the expanded receptor specificity of H9N2 has raised concerns as a possible source of a novel human influenza virus [33][34].
From 2003 to 2017, sporadic human infections caused by H5N1, H7N7, and H7N9 AIVs have been observed in different European and Asian countries [35][36][37][38][39][40]. Since 2013, newly emerging AIVs have frequently crossed the species barrier to infect humans, causing several fatal infections [41][42][43][44][45].
Overall, it has to be considered that both continuous influenza virus genetic evolution and the actual environment of human activities may facilitate the occurrence of zoonoses with a high transmissibility level, as evidenced by the recent SARS-CoV-2 pandemic. Moreover, highly pathogenic AIVs have never circulated extensively among humans; therefore, the lack of pre-existing immunity poses the human population with a high risk of severe influenza occurrence.

2. The Cellular Cytoskeleton

The cytoskeleton of eukaryotic cells is a well-organized and highly dynamic filamentous network that radiates through the cell and primarily comprises three filament types that function co-ordinately: actin filaments (microfilaments), microtubules, and intermediate filaments [46]. Septins are a family of GTPases and are considered the fourth cytoskeleton component [47]. Cellular motor proteins, such as dynein, kinesin, myosin, and other accessory proteins, represent a structurally and functionally diverse family of molecules that actively concur with cytoskeletal functions, facilitating the capture and transport of a variety of cargo along cytoskeletal networks.
A complex cytoskeletal network connects the plasma membrane to the nucleus and carries out diverse roles [48]. Specifically, the cytoskeleton contributes to cell morphology regulation, cell migration, apoptosis, cell differentiation, and cell division [46][49][50][51][52][53]. Importantly, all cytoskeletal components can swiftly adapt to both external and intracellular stimuli, undergoing rapid and continuous structural modifications [54].
Microfilaments are thin and fibrous structures responsible for cytoplasmic streaming and represent the major structural component of the cell. They concentrate under the plasma membrane, are involved in cell division, maintain the plasma membrane structure, and participate in intracellular trafficking and cell motility. Several actin-binding proteins connect actin filaments, while other actin-binding proteins allow the interaction of actin with specific cytoskeleton components [55]. Microfilaments are considered the most dynamic cytoskeletal networks, as they can undergo rapid and significant depolymerization when cell deformation and movement are required [54][56]. Specifically, cortical actin is primarily implied in events related to the presentation of cell membrane molecules, endocytosis, and viral entry/exit mechanisms [57], while nuclear actin regulates chromatin remodeling and gene transcription mechanisms [58].
Microtubules are highly dynamic polymers of tubulin subjected to rapid cycles of polymerization and subsequent depolymerization, depending on the requirements of the cell [59]. Microtubules radiate from the centrosome, the microtubule-organizing center of eukaryotic cells [60]. They are involved in cell motility, signal transduction, the subcellular distribution of organelles, and intracellular transport [61]. Several microtubule-binding proteins regulate microtubule dynamics [62]. Both actin and microtubules form polarized filaments with growing plus-ends pointed toward the plasma membrane, allowing the ATP-mediated directional transport of cargo such as vesicles and organelles. Specifically, actin is generally involved in the short-range transport near the cytoplasmic membrane, while microtubules are for the long-range intracellular transport.
The largest gene family encodes the intermediate filaments (IFs). IFs are found in the cytoplasm and are adjacent to the inner face of the nuclear envelope. Comprised of more than 70 components, they show a remarkable diversity, and provide mechanical strength to animal cells, maintaining the cell shape and tension, and protecting the genome. Major IFs are classified into five types, based on their structural composition and origin: keratin, desmin, glial fibrillary acidic protein, vimentin, and neurofilament protein [63]. Keratins are the main components of the cytoskeleton in epithelial and mesenchymal cells. Keratins are classified into two groups, based on differential immunogenicity properties. They provide structural support to cells and counteract the effects of physical stress on cell integrity. Vimentin is assembled into major cytoskeletal systems in cells of mesenchymal and ectodermal origin. Recent evidence has shown that vimentin and filamentous actin form interpenetrating networks in the cell cortex and vimentin participates in the regulation of actin dynamics [64]. The intracellular distribution of vimentin allows the structural maintenance of cell organelles. Moreover, vimentin is an integrator of cellular mechanical processes, promptly responding to cellular stress [65].
Lamins are nuclear IFs and the principal component of the nuclear lamina, a mesh of proteins inside the inner nuclear membrane [66]. Lamins maintain the structural integrity of the nucleus and anchor the chromatin and nuclear pore complexes to the nuclear periphery [67]. In association with actin and actin motor proteins, these proteins mainly constitute the nuclear cytoskeleton [68]. Of note, they are involved in key roles, such as the regulation of nuclear morphology, stability, gene expression, and transmitting and deciphering mechanical stimuli into physiological responses.
Overall, the cytoskeletal scaffold regulates numerous aspects of cell biology, undergoing rapid and continuous structural changes to satisfy the requirements of the cell in both physiological and pathological conditions. Viruses represent an excellent tool to study the regulatory mechanisms of the cellular cytoskeleton.
Viruses are obligate intracellular parasites that depend strictly on the host cell machinery to perform their successful replication [46][69][70][71]. Specifically, the cytoskeleton provides a scaffold for viral entry, sub-cellular trafficking through the dense cytosol, replication, assembly, and egression [72]. Viruses can subvert and exploit physiological cytoskeletal functions to promote their replication, with varying effects, depending on the virus species involved. The complexity of the cellular cytoskeleton and the differences between the replication cycles of human viruses belonging to different families allow very different types of interactions, which remain poorly described. The contribution of the cytoskeleton in the replication cycle of viruses is critical to expand our knowledge of virus-coopted regulatory mechanisms, which could allow the discovery of potential therapeutic strategies.
To date, considerable research activities have attempted to understand the pathogenicity and mechanisms of transmission of AIVs, focusing on the influenza virus themselves. Therefore, a comprehensive understanding of the response of host factors during viral pathogenesis in mammals is needed. In this way, characterizing the complex molecular mechanisms linking the cell cytoskeleton to influenza virus infection provides insights into the main filament network alterations, which might be useful for successful virus replication and transmission.

3. The Involvement of the Cellular Cytoskeleton in Influenza Virus Infection

In influenza virus infection, several cytoskeletal proteins exert a key regulatory role during internalization, endosomal acidification, and virus intracellular transport mechanisms [73][74]. It has been shown that endosomes containing influenza viruses co-localize with microfilaments and undergo further movements, suggesting the intervention of myosin motor proteins [75][76]. Myosin is also involved when influenza virus entry occurs through micropinocytosis [77]. In addition, keratin participates in the early cytoplasmic transport of influenza virus [78].
In the second step, the influenza virus intracytoplasmic transport switches from microfilaments to microtubules and the associated dynein motor protein, allowing the release of viral ribonucleoproteins near the nucleus, the site of viral genome replication [59][79][80]. It has been shown that intact microtubules promote both influenza virus entry to and exit from the host cell [76][81][82].
Vimentin regulates the activity and intracellular transport of IAVs, also exerting critical roles in the host cell response [74][83]. Specifically, it has been assessed that vimentin might play an important role in the regulation of lipids during H9N2 replication, providing an important antiviral target against the influenza virus [84]. Moreover, it has been shown that the integrity of IFs affects the release of H7N1 AIV progeny in mammalian cells, leading to decreased viral replication efficiency [85].
In the late phases of infection, the microfilaments regulate the distribution of newly synthesized influenza virus proteins at the plasma membrane, with the parallel involvement of myosin, contributing to viral assembly and budding [86][87].
Figure 1 shows the phases of the IAV replication cycle requiring the active participation of the cellular cytoskeleton.
Figure 1. Cytoskeleton involvement during IAV replication. The Figure has been created with (accessed on 6 March 2024).
The cell-dependent highly dynamic or polymerized state of the cytoskeleton and the associated regulatory proteins may regulate the exit of influenza virus infection. In this regard, mammalian Diaphanous-related formin-1, a Rho-effector protein generating linear actin filaments and regulating microtubule organization, represents a restriction factor that counteracts cytoskeleton dynamics during the early phases of IAV infection [88]. In addition, it has been shown that highly polymerized/stable microfilaments and microtubules may restrict the early phases of IAV infection [75][85].
Notably, the influenza virus can modulate the dynamics of different cytoskeletal filaments by promoting their remodeling to support viral replication [89]. In this regard, the IAV can subvert the structural organization of cytokeratin 8, enhancing its phosphorylation state and thereby promoting its replicative efficiency [90]. Moreover, it has been assessed that the influenza virus stimulated the phosphorylation of cytoskeletal ezrin, radixin, and moesin, inducing structural cytoskeletal changes and permeability increases in pulmonary microvascular endothelial cells that favor its replication [91].
These observations strongly support the contribution of specific components of the cellular cytoskeleton to the replication of influenza viruses. Their intervention has some degree of variability, depending on both the cell type and the viral strain involved, attesting to the uniqueness of the influenza virus–host cell relationship.


  1. Swayne, D.E.; Suarez, D.L. Highly pathogenic avian influenza. Rev. Sci. Tech. 2000, 19, 463–482.
  2. Chen, J.; Lee, K.H.; Steinhauer, D.A.; Stevens, D.J.; Skehel, J.J.; Wiley, D.C. Structure of the hemagglutinin precursor cleavage site, a determinant of influenza pathogenicity and the origin of the labile conformation. Cell 1998, 95, 409–417.
  3. Escalera-Zamudio, M.; Golden, M.; Gutiérrez, B.; Thézé, J.; Keown, J.R.; Carrique, L.; Bowden, T.A.; Pybus, O.G. Parallel evolution in the emergence of highly pathogenic avian influenza A viruses. Nat Commun 2020, 11, 5511.
  4. Centers for Disease Control and Prevention. Available online: (accessed on 31 January 2024).
  5. World Health Organization. Influenza Fact Sheet. Available online: (accessed on 3 October 2023).
  6. Gao, R.; Cao, B.; Hu, Y.; Feng, Z.; Wang, D.; Hu, W.; Chen, J.; Jie, Z.; Qiu, H.; Xu, K.; et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N. Engl. J. Med. 2013, 368, 1888–1897.
  7. Jiang, L.; Chen, H.; Li, C. Advances in deciphering the interactions between viral proteins of influenza A virus and host cellular proteins. Cell Insight 2023, 2, 100079.
  8. Webster, R.G. Predictions for future human influenza pandemics. J. Infect. Dis. 1997, 176, S14–S19.
  9. Webster, R.G. Influenza virus: Transmission between species and relevance to emergence of the next human pandemic. Arch. Virol. Suppl. 1997, 13, 105–113.
  10. Webby, R.J.; Webster, R.G. Are we ready for pandemic influenza? Science 2003, 302, 1519–1522.
  11. de Graaf, M.; Fouchier, R.A. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. EMBO J. 2014, 33, 823–841.
  12. Steel, J.; Lowen, A.C.; Mubareka, S.; Palese, P. Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog. 2009, 5, e1000252.
  13. Huang, X.; Zheng, M.; Wang, P.; Mok, B.W.; Liu, S.; Lau, S.Y.; Chen, P.; Liu, Y.C.; Liu, H.; Chen, Y.; et al. An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells. Nat. Commun. 2017, 8, 14751.
  14. Du, W.; de Vries, E.; van Kuppeveld, F.J.M.; Matrosovich, M.; de Haan, C.A.M. Second sialic acid-binding site of influenza A virus neuraminidase: Binding receptors for efficient release. FEBS J. 2021, 288, 5598–5612.
  15. Vourc’h, G.; Moutou, F.; Morand, S.; Jourdain, E. Zoonoses the Ties that Bind Humans to Animals ; Éditions Quae: Versailles, France, 2022.
  16. Chen, H.; Smith, G.J.; Li, K.S.; Wang, J.; Fan, X.H.; Rayner, J.M.; Vijaykrishna, D.; Zhang, J.X.; Zhang, L.J.; Guo, C.T.; et al. Establishment of multiple sublineages of H5N1 influenza virus in Asia: Implications for pandemic control. Proc. Natl. Acad. Sci. USA 2006, 103, 2845–2850.
  17. Yuen, K.Y.; Chan, P.K.; Peiris, M.; Tsang, D.N.; Que, T.L.; Shortridge, K.F.; Cheung, P.T.; To, W.K.; Ho, E.T.; Sung, R.; et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 1998, 351, 467–471.
  18. Claas, E.C.; de Jong, J.C.; van Beek, R.; Rimmelzwaan, G.F.; Osterhaus, A.D. Human influenza virus A/HongKong/156/97 (H5N1) infection. Vaccine 1998, 16, 977–978.
  19. Bridges, C.B.; Lim, W.; Hu-Primmer, J.; Sims, L.; Fukuda, K.; Mak, K.H.; Rowe, T.; Thompson, W.W.; Conn, L.; Lu, X.; et al. Risk of influenza A (H5N1) infection among poultry workers, Hong Kong, 1997–1998. J. Infect. Dis. 2002, 185, 1005–1010.
  20. Katz, J.M.; Lim, W.; Bridges, C.B.; Rowe, T.; Hu-Primmer, J.; Lu, X.; Abernathy, R.A.; Clarke, M.; Conn, L.; Kwong, H.; et al. Antibody response in individuals infected with avian influenza A (H5N1) viruses and detection of anti-H5 antibody among household and social contacts. J. Infect. Dis. 1999, 180, 1763–1770.
  21. Bahgat, M.M.; Kutkat, M.A.; Nasraa, M.H.; Mostafa, A.; Webby, R.; Bahgat, I.M.; Ali, M.A. Characterization of an avian influenza virus H5N1 Egyptian isolate. J. Virol. Methods 2009, 159, 244–250.
  22. World Health Organization. Cumulative Number of Confirmed Human Cases for Avian Influenza A (H5N1) Reported to WHO, 2003–2023. 2023. Available online: (accessed on 26 January 2024).
  23. Xie, R.; Edwards, K.M.; Wille, M.; Wei, X.; Wong, S.S.; Zanin, M.; El-Shesheny, R.; Ducatez, M.; Poon, L.L.M.; Kayali, G.; et al. The episodic resurgence of highly pathogenic avian influenza H5 virus. Nature 2023, 622, 810–817.
  24. Monne, I.; Yamage, M.; Dauphin, G.; Claes, F.; Ahmed, G.; Giasuddin, M.; Salviato, A.; Ormelli, S.; Bonfante, F.; Schivo, A.; et al. Reassortant avian influenza A (H5N1) viruses with H9N2-PB1 gene in poultry, Bangladesh. Emerg. Infect. Dis. 2013, 19, 1630–1634.
  25. Gerloff, N.A.; Khan, S.U.; Balish, A.; Shanta, I.S.; Simpson, N.; Berman, L.; Haider, N.; Poh, M.K.; Islam, A.; Gurley, E.; et al. Multiple reassortment events among highly pathogenic avian influenza A(H5N1) viruses detected in Bangladesh. Virology 2014, 450–451, 297–307.
  26. Li, Y.; Shi, J.; Zhong, G.; Deng, G.; Tian, G.; Ge, J.; Zeng, X.; Song, J.; Zhao, D.; Liu, L.; et al. Continued evolution of H5N1 influenza viruses in wild birds, domestic poultry, and humans in China from 2004 to 2009. J. Virol. 2010, 84, 8389–8397.
  27. Li, Z.; Chen, H.; Jiao, P.; Deng, G.; Tian, G.; Li, Y.; Hoffmann, E.; Webster, R.G.; Matsuoka, Y.; Yu, K. Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J. Virol. 2005, 79, 12058–12064.
  28. Hatta, M.; Gao, P.; Halfmann, P.; Kawaoka, Y. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001, 293, 1840–1842.
  29. Pan, M.; Gao, R.; Lv, Q.; Huang, S.; Zhou, Z.; Yang, L.; Li, X.; Zhao, X.; Zou, X.; Tong, W.; et al. Human infection with a novel, highly pathogenic avian influenza A (H5N6) virus: Virological and clinical findings. J. Infect. 2016, 72, 52–59.
  30. Matrosovich, M.N.; Krauss, S.; Webster, R.G. H9N2 influenza A viruses from poultry in Asia have human virus-like receptor specificity. Virology 2001, 281, 156–162.
  31. Liu, N.; Song, W.; Wang, P.; Lee, K.; Chan, W.; Chen, H.; Cai, Z. Proteomics analysis of differential expression of cellular proteins in response to avian H9N2 virus infection in human cells. Proteomics 2008, 8, 1851–1858.
  32. Butt, K.M.; Smith, G.J.; Chen, H.; Zhang, L.J.; Leung, Y.H.; Xu, K.M.; Lim, W.; Webster, R.G.; Yuen, K.Y.; Peiris, J.S.; et al. Human infection with an avian H9N2 influenza A virus in Hong Kong in 2003. J. Clin. Microbiol. 2005, 43, 5760–5767.
  33. Ha, Y.; Stevens, D.J.; Skehel, J.J.; Wiley, D.C. X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs. Proc. Natl. Acad. Sci. USA 2001, 98, 11181–11186.
  34. Huang, R.; Liu, J.; Liang, W.; Wang, A.; Liu, Z.; Yang, Y.; Lv, J.; Bao, Y.; Gao, Y.; Miao, Z.; et al. Response profiles of cytokines and chemokines against avian H9N2 influenza virus within the mouse lung. Med. Microbiol. Immunol. 2014, 203, 109–114.
  35. Ungchusak, K.; Auewarakul, P.; Dowell, S.F.; Kitphati, R.; Auwanit, W.; Puthavathana, P.; Uiprasertkul, M.; Boonnak, K.; Pittayawonganon, C.; Cox, N.J.; et al. Probable person-to-person transmission of avian influenza A (H5N1). N. Engl. J. Med. 2005, 352, 333–340.
  36. Kandun, I.N.; Wibisono, H.; Sedyaningsih, E.R.; Yusharmen; Hadisoedarsuno, W.; Purba, W.; Santoso, H.; Septiawati, C.; Tresnaningsih, E.; Heriyanto, B.; et al. Three Indonesian clusters of H5N1 virus infection in 2005. N. Engl. J. Med. 2006, 355, 2186–2194.
  37. Wang, H.; Feng, Z.; Shu, Y.; Yu, H.; Zhou, L.; Zu, R.; Huai, Y.; Dong, J.; Bao, C.; Wen, L.; et al. Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. Lancet 2008, 371, 1427–1434.
  38. Li, Q.; Zhou, L.; Zhou, M.; Chen, Z.; Li, F.; Wu, H.; Xiang, N.; Chen, E.; Tang, F.; Wang, D.; et al. Epidemiology of human infections with avian influenza A(H7N9) virus in China. N. Engl. J. Med. 2014, 370, 520–532.
  39. Zhang, Z.H.; Meng, L.S.; Kong, D.H.; Liu, J.; Li, S.Z.; Zhou, C.; Sun, J.; Song, R.J.; Wu, J.J. A Suspected Person-to-person Transmission of Avian Influenza A (H7N9) Case in Ward. Chin. Med. J. 2017, 130, 1255–1256.
  40. Du Ry van Beest Holle, M.; Meijer, A.; Koopmans, M.; de Jager, C.M. Human-to-human transmission of avian influenza A/H7N7, The Netherlands, 2003. Eurosurveillance 2005, 10, 3–4.
  41. Parry, J. H7N9 avian flu infects humans for the first time. BMJ 2013, 346, f2151.
  42. To, K.K.; Tsang, A.K.; Chan, J.F.; Cheng, V.C.; Chen, H.; Yuen, K.Y. Emergence in China of human disease due to avian influenza A(H10N8)—Cause for concern? J. Infect. 2014, 68, 205–215.
  43. Shi, W.; Shi, Y.; Wu, Y.; Liu, D.; Gao, G.F. Origin and molecular characterization of the human-infecting H6N1 influenza virus in Taiwan. Protein Cell 2013, 4, 846–853.
  44. Wu, A.; Su, C.; Wang, D.; Peng, Y.; Liu, M.; Hua, S.; Li, T.; Gao, G.F.; Tang, H.; Chen, J.; et al. Sequential reassortments underlie diverse influenza H7N9 genotypes in China. Cell Host Microbe 2013, 14, 446–452.
  45. Qi, W.; Zhou, X.; Shi, W.; Huang, L.; Xia, W.; Liu, D.; Li, H.; Chen, S.; Lei, F.; Cao, L.; et al. Genesis of the novel human-infecting influenza A(H10N8) virus and potential genetic diversity of the virus in poultry, China. Eurosurveillance 2014, 19, 20841.
  46. Li, M.; Peng, D.; Cao, H.; Yang, X.; Li, S.; Qiu, H.J.; Li, L.F. The Host Cytoskeleton Functions as a Pleiotropic Scaffold: Orchestrating Regulation of the Viral Life Cycle and Mediating Host Antiviral Innate Immune Responses. Viruses 2023, 15, 1354.
  47. Mostowy, S.; Cossart, P. Septins: The fourth component of the cytoskeleton. Nat. Rev. Mol. Cell Biol. 2012, 13, 183–194.
  48. Liu, L.; Luo, Q.; Sun, J.; Song, G. Nucleus and nucleus-cytoskeleton connections in 3D cell migration. Exp. Cell Res. 2016, 348, 56–65.
  49. Fuchs, E.; Cleveland, D.W. A structural scaffolding of intermediate filaments in health and disease. Science 1998, 279, 514–519.
  50. Słońska, A.; Polowy, R.; Golke, A.; Cymerys, J. Role of cytoskeletal motor proteins in viral infection. Postepy Hig. Med. Dosw. 2012, 66, 810–817.
  51. MacTaggart, B.; Kashina, A. Posttranslational modifications of the cytoskeleton. Cytoskeleton 2021, 78, 142–173.
  52. Buxboim, A.; Kronenberg-Tenga, R.; Salajkova, S.; Avidan, N.; Shahak, H.; Thurston, A.; Medalia, O. Scaffold, mechanics and functions of nuclear lamins. FEBS Lett. 2023, 597, 2791–2805.
  53. Buchwalter, A. Intermediate, but not average: The unusual lives of the nuclear lamin proteins. Curr. Opin. Cell Biol. 2023, 84, 102220.
  54. Hohmann, T.; Dehghani, F. The Cytoskeleton-A Complex Interacting Meshwork. Cells 2019, 8, 362.
  55. Pollard, T.D.; Cooper, J.A. Actin and actin-binding proteins. A critical evaluation of mechanisms and functions. Annu. Rev. Biochem. 1986, 55, 987–1035.
  56. Carlier, M.F.; Shekhar, S. Global treadmilling coordinates actin turnover and controls the size of actin networks. Nat. Rev. Mol. Cell Biol. 2017, 18, 389–401.
  57. Davidson, P.M.; Cadot, B. Actin on and around the Nucleus. Trends Cell Biol. 2021, 31, 211–223.
  58. Kloc, M.; Wilk, K.; Vargas, D.; Shirato, Y.; Bilinski, S.; Etkin, L.D. Potential structural role of non-coding and coding RNAs in the organization of the cytoskeleton at the vegetal cortex of Xenopus oocytes. Development 2005, 132, 3445–3457.
  59. Simpson, C.; Yamauchi, Y. Microtubules in Influenza Virus Entry and Egress. Viruses 2020, 12, 117.
  60. Rieder, C.L.; Faruki, S.; Khodjakov, A. The centrosome in vertebrates: More than a microtubule-organizing center. Trends Cell Biol. 2001, 11, 413–419.
  61. Gudimchuk, N.B.; McIntosh, J.R. Regulation of microtubule dynamics, mechanics and function through the growing tip. Nat. Rev. Mol. Cell. Biol. 2021, 22, 777–795.
  62. Guru, A.; Saravanan, S.; Sharma, D.; Narasimha, M. The microtubule end-binding proteins EB1 and Patronin modulate the spatiotemporal dynamics of myosin and pattern pulsed apical constriction. Development 2022, 149, dev199759.
  63. Ramaekers, F.C.; Bosman, F.T. The cytoskeleton and disease. J. Pathol. 2004, 204, 351–354.
  64. Wu, H.; Shen, Y.; Sivagurunathan, S.; Weber, M.S.; Adam, S.A.; Shin, J.H.; Fredberg, J.J.; Medalia, O.; Goldman, R.; Weitz, D.A. Vimentin intermediate filaments and filamentous actin form unexpected interpenetrating networks that redefine the cell cortex. Proc. Natl. Acad. Sci. USA 2022, 119, e2115217119.
  65. Redmond, C.J.; Coulombe, P.A. Intermediate filaments as effectors of differentiation. Curr. Opin. Cell Biol. 2021, 68, 155–162.
  66. Odell, J.; Lammerding, J. Lamins as structural nuclear elements through evolution. Curr. Opin. Cell Biol. 2023, 85, 102267.
  67. Aebi, U.; Cohn, J.; Buhle, L.; Gerace, L. The nuclear lamina is a meshwork of intermediate-type filaments. Nature 1986, 323, 560–564.
  68. Maly, I.V.; Hofmann, W.A. Myosins in the Nucleus. Adv. Exp. Med. Biol. 2020, 1239, 199–231.
  69. da Silva, E.S.; Naghavi, M.H. Microtubules and viral infection. Adv. Virus Res. 2023, 115, 87–134.
  70. Horníková, L.; Bruštíková, K.; Huérfano, S.; Forstová, J. Nuclear Cytoskeleton in Virus Infection. Int. J. Mol. Sci. 2022, J23, 578.
  71. Wang, I.H.; Burckhardt, C.J.; Yakimovich, A.; Greber, U.F. Imaging, Tracking and Computational Analyses of Virus Entry and Egress with the Cytoskeleton. Viruses 2018, 10, 166.
  72. Radtke, K.; Döhner, K.; Sodeik, B. Viral interactions with the cytoskeleton: A hitchhiker’s guide to the cell. Cell. Microbiol. 2006, 8, 387–400.
  73. Sun, X.; Whittaker, G.R. Role of the actin cytoskeleton during influenza virus internalization into polarized epithelial cells. Cell. Microbiol. 2007, 9, 1672–1682.
  74. Wu, W.; Panté, N. Vimentin plays a role in the release of the influenza A viral genome from endosomes. Virology 2016, 497, 41–52.
  75. De Conto, F.; Di Lonardo, E.; Arcangeletti, M.C.; Chezzi, C.; Medici, M.C.; Calderaro, A. Highly dynamic microtubules improve the effectiveness of early stages of human influenza A/NWS/33 virus infection in LLC-MK2 cells. PLoS ONE 2012, 7, e41207.
  76. Lakadamyali, M.; Rust, M.J.; Babcock, H.P.; Zhuang, X. Visualizing infection of individual influenza viruses. Proc. Natl. Acad. Sci. USA 2003, 100, 9280–9285.
  77. de Vries, E.; Tscherne, D.M.; Wienholts, M.J.; Cobos-Jiménez, V.; Scholte, F.; García-Sastre, A.; Rottier, P.J.; de Haan, C.A. Dissection of the influenza A virus endocytic routes reveals macropinocytosis as an alternative entry pathway. PLoS Pathog. 2011, 7, e1001329.
  78. Huang, X.; Yin, G.; Zhou, B.; Cai, Y.; Hu, J.; Huang, J.; Chen, Z.; Liu, Q.; Feng, X. KRT10 plays an important role in the release of viral genome from endosomes during H9N2 subtype AIV replication in HeLa cells. Vet. Microbiol. 2023, 284, 109824.
  79. Zhang, L.J.; Xia, L.; Liu, S.L.; Sun, E.Z.; Wu, Q.M.; Wen, L.; Zhang, Z.L.; Pang, D.W. A “Driver Switchover” Mechanism of Influenza Virus Transport from Microfilaments to Microtubules. ACS Nano 2018, 12, 474–484.
  80. Greber, U.F.; Way, M. A superhighway to virus infection. Cell 2006, 124, 741–754.
  81. Rust, M.J.; Lakadamyali, M.; Zhang, F.; Zhuang, X. Assembly of endocytic machinery around individual influenza viruses during viral entry. Nat. Struct. Mol. Biol. 2004, 11, 567–573.
  82. Hodgson, L.; Verkade, P.; Yamauchi, Y. Correlative Light and Electron Microscopy of Influenza Virus Entry and Budding. Methods Mol. Biol. 2018, 1836, 237–260.
  83. Ramos, I.; Stamatakis, K.; Oeste, C.L.; Pérez-Sala, D. Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections. Int. J. Mol. Sci. 2020, 21, 4675.
  84. Lu, A.; Yang, J.; Huang, X.; Huang, X.; Yin, G.; Cai, Y.; Feng, X.; Zhang, X.; Li, Y.; Liu, Q. The Function behind the Relation between Lipid Metabolism and Vimentin on H9N2 Subtype AIV Replication. Viruses 2022, 14, 1814.
  85. Arcangeletti, M.C.; De Conto, F.; Ferraglia, F.; Pinardi, F.; Gatti, R.; Orlandini, G.; Covan, S.; Motta, F.; Rodighiero, I.; Dettori, G.; et al. Host-cell-dependent role of actin cytoskeleton during the replication of a human strain of influenza A virus. Arch. Virol. 2008, 153, 1209–1221.
  86. Simpson-Holley, M.; Ellis, D.; Fisher, D.; Elton, D.; McCauley, J.; Digard, P. A functional link between the actin cytoskeleton and lipid rafts during budding of filamentous influenza virions. Virology 2002, 301, 212–225.
  87. Kumakura, M.; Kawaguchi, A.; Nagata, K. Actin-myosin network is required for proper assembly of influenza virus particles. Virology 2015, 476, 141–150.
  88. De Conto, F.; Fazzi, A.; Razin, S.V.; Arcangeletti, M.C.; Medici, M.C.; Belletti, S.; Chezzi, C.; Calderaro, A. Mammalian Diaphanous-related formin-1 restricts early phases of influenza A/NWS/33 virus (H1N1) infection in LLC-MK2 cells by affecting cytoskeleton dynamics. Mol. Cell. Biochem. 2018, 437, 185–201.
  89. Bedi, S.; Ono, A. Friend or Foe: The Role of the Cytoskeleton in Influenza A Virus Assembly. Viruses 2019, 11, 46.
  90. De Conto, F.; Conversano, F.; Razin, S.V.; Belletti, S.; Arcangeletti, M.C.; Chezzi, C.; Calderaro, A. Host-cell dependent role of phosphorylated keratin 8 during influenza A/NWS/33 virus (H1N1) infection in mammalian cells. Virus Res. 2021, 295, 198333.
  91. Zhang, C.; Wu, Y.; Xuan, Z.; Zhang, S.; Wang, X.; Hao, Y.; Wu, J.; Zhang, S. p38MAPK, Rho/ROCK and PKC pathways are involved in influenza-induced cytoskeletal rearrangement and hyperpermeability in PMVEC via phosphorylating ERM. Virus Res. 2014, 192, 6–15.
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