The Host Cytoskeleton Functions as a Pleiotropic Scaffold: Orchestrating Regulation of the Viral Life Cycle and Mediating Host Antiviral Innate Immune Responses

Abstract

Viruses are obligate intracellular parasites that critically depend on their hosts to initiate infection, complete replication cycles, and generate new progeny virions. To achieve these goals, viruses have evolved numerous elegant strategies to subvert and utilize different cellular machinery. The cytoskeleton is often one of the first components to be hijacked as it provides a convenient transport system for viruses to enter the cell and reach the site of replication. The cytoskeleton is an intricate network involved in controlling the cell shape, cargo transport, signal transduction, and cell division. The host cytoskeleton has complex interactions with viruses during the viral life cycle, as well as cell-to-cell transmission once the life cycle is completed. Additionally, the host also develops unique, cytoskeleton-mediated antiviral innate immune responses. These processes are also involved in pathological damages, although the comprehensive mechanisms remain elusive. In this review, we briefly summarize the functions of some prominent viruses in inducing or hijacking cytoskeletal structures and the related antiviral responses in order to provide new insights into the crosstalk between the cytoskeleton and viruses, which may contribute to the design of novel antivirals targeting the cytoskeleton.

Avian Influenza A Viruses Modulate the Cellular Cytoskeleton during Infection of Mammalian Hosts

“…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 [ 52 ]. Septins are a family of GTPases and are considered the fourth cytoskeleton component [ 53 ].…”

“…A complex cytoskeletal network connects the plasma membrane to the nucleus and carries out diverse roles [ 54 ]. Specifically, the cytoskeleton contributes to cell morphology regulation, cell migration, apoptosis, cell differentiation, and cell division [ 52 , 55 , 56 , 57 , 58 , 59 ]. Importantly, all cytoskeletal components can swiftly adapt to both external and intracellular stimuli, undergoing rapid and continuous structural modifications [ 60 ].…”

“…Viruses are obligate intracellular parasites that depend strictly on the host cell machinery to perform their successful replication [ 52 , 75 , 76 , 77 ]. Specifically, the cytoskeleton provides a scaffold for viral entry, sub-cellular trafficking through the dense cytosol, replication, assembly, and egression [ 78 ].…”

“…Consequently, the virus-induced actin disturbance is considered a priming signal for innate immunity activation [ 107 ]. Therefore, it appears conceivable that the cellular cytoskeleton carries out two strictly interconnected functions: it may both help viruses during their replication cycle and assist cells in activating the innate immunity mechanisms to provide rapid frontline defense [ 52 ]. The latter aspect is mainly achieved by using specific pattern-recognition receptors [ 109 , 110 ].…”

Special Issue: “Innate Immunity to Virus Infection, 1st Edition”

“…Alves et al summarized how placental cells engaged in innate immune responses play roles in response to Dengue virus (DENV) and chikungunya (CHIKV) infections [ 9 ]. Li et al reported the roles of various well-known viruses in hijacking cytoskeletal structures and the accompanying antiviral responses [ 10 ]. Roldan et al described the comprehensive understanding of the possible mechanisms of anti-cytokine autoantibody production, which could improve the approach to treating some infections, not only targeting pathogens but as a treatment for some autoimmunity patients [ 11 ].…”