Cytoskeleton—a crucial key in host cell for coronavirus infection

Abstract

The emerging coronavirus pandemic is threatening the public health all over the world. Cytoskeleton is an intricate network involved in controlling cell shape, cargo transport, signal transduction, and cell division. Infection biology studies have illuminated essential roles for cytoskeleton in mediating the outcome of host‒virus interactions. In this review, we discuss the dynamic interactions between actin filaments, microtubules, intermediate filaments, and coronaviruses. In one round of viral life cycle, coronaviruses surf along filopodia on the host membrane to the entry sites, utilize specific intermediate filament protein as co-receptor to enter target cells, hijack microtubules for transportation to replication and assembly sites, and promote actin filaments polymerization to provide forces for egress. During coronavirus infection, disruption of host cytoskeleton homeostasis and modification state is tightly connected to pathological processes, such as defective cytokinesis, demyelinating, cilia loss, and neuron necrosis. There are increasing mechanistic studies on cytoskeleton upon coronavirus infection, such as viral protein‒cytoskeleton interaction, changes in the expression and post-translation modification, related signaling pathways, and incorporation with other host factors. Collectively, these insights provide new concepts for fundamental virology and the control of coronavirus infection.

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

“…Another central class of genes identified in our LOF screen were components involved with cytoskeletal rearrangement (ROCK1) and cell-cell junctions (E-cadherin). Viruses commonly coopt actin or microtubule components and motor proteins to shuttle viral components around the cell and enable efficient replication (Arons et al, 2020; Taylor et al, 2011; Wen et al, 2020). Beyond intracellular shuttling, some viruses hijack host cytoskeletal components as well as cellcell protein complexes for cell-cell spread (Bergelson, 2009; Bouhaddou et al, 2020; Gordon et al, 2020; Mothes et al, 2010).…”

Role of Tunneling Nanotubes in Viral Infection, Neurodegenerative Disease, and Cancer

“…In fact, the co-culture of cells expressing spike glycoproteins of SARS-CoV-2, along with the cells expressing human ACE-2 and heparan sulfate especially at the tips, resulted in induction of the widely distributed TNTs between cells ( Figure 7 ). The presence of TNTs during SARS-CoV-2 infection is supported by an upregulation of casein kinase II (CK2) ( 89 ) and heparan sulfate ( 87 ), a key enhancer of actin cytoskeleton and the cellular receptor for virus entry may have far reaching clinical outcomes with profound and widespread dissemination of SARS-CoV-2 via TNTs affecting multiple organs and the disease severity as consistently observed with COVID-19 patients ( 82 ). Clearly, understanding the hijacking of host cell TNTs by SARS-CoV-2 during an early or late stage of infection seems worthy of future investigation in order to develop effective measures towards therapeutics and prophylactics.…”

“…SARS-CoV-2 induced surface disruption at the level of the host cell's actin cytoskeleton legitimizes the potential that other surface perturbations, such as the eruption of F-actin containing TNT bridges at the cell surface, may assist SARS-CoV-2 widespread dissemination. In fact, previous studies have shown that the cytoskeleton network plays an important role during the entry, replication, and maturation process of coronaviruses, including SARS-CoV-2 (Figure 6) (79,88,89). A recent study by Caldas et al, 2020 provided the first evidence of the SARS-CoV-2 mediated viral surfing on filopodium and the occurrence of a thin (< 0.7 mm) strand of F-actin containing tunneling nanotube (TNT) using high resolution electron microscopy (79).…”

“…Viral progeny, while frequently disseminated from hijacked cells via exocytosis, may also collect in these localized regions for transport via actin-rich bridges, like TNTs, across cells. Similarly, other single-stranded RNA viruses have demonstrated TNT developmental behaviors, including the gastroenteritis virus (TGEV) which has been found to induce F-actin polymerization, or protrusive growths from the cell surface, and SARS-CoV and murine hepatitis virus, which induce cell membrane interruptions and filopodia formation like the CK2 protrusions off SARS-CoV-2 infected cells ( 89 ). This evidence suggests that SARS-CoV-2, like many of the viruses to which it is related, uses TNTs to propagate its pathogenesis, which may offer some insights into its ability to affect multiple organs and cause a diverse array of complications throughout the body.…”

Vitamin D binding protein: A polymorphic protein with actin-binding capacity in COVID-19

“…Focussing on the cytoskeleton, in one round of viral life cycle, coronaviruses promote actin filament polymerization to provide forces for egress [9] . In catabolic conditions, e.g., sepsis and acute respiratory distress syndrome (ARDS), tissue damage leads to the release of globular actin (G-actin) to the extracellular environment and the circulation.…”