Virus interactions with the actin cytoskeleton—what we know and do not know about SARS-CoV-2

Kloc, Małgorzata; Uosef, Ahmed; Wosik, J.; Kubiak, Jacek Z.; Ghobrial, Rafik M.

doi:10.1007/s00705-022-05366-1

Cited by 37 publications

(20 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We speculate that TNTs accelerate the propagation of the infection, even between permissive cells. Because TNTs are dynamic transient structures ( 28 ) where actin is able to polymerize and depolymerize rapidly (i.e., 30 to 60 s) ( 68 , 69 ), the virus could potentially spread faster through TNTs than through other routes ( 67 ). Previous evidence indicated that upon interaction with cellular protrusions, viruses undergo rapid actin- and myosin II–mediated transport by “surfing” on the cell surface before reaching entry sites closer to the cell body ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Tunneling nanotubes provide a route for SARS-CoV-2 spreading

et al. 2022

View full text Add to dashboard Cite

Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represent a major issue in long coronavirus disease. How SARS-CoV-2 gains access to the brain and how infection leads to neurological symptoms are not clear because the principal means of viral entry by endocytosis, the angiotensin-converting enzyme 2 receptor, are barely detectable in the brain. We report that human neuronal cells, nonpermissive to infection through the endocytic pathway, can be infected when cocultured with permissive infected epithelial cells. SARS-CoV-2 induces the formation of tunneling nanotubes (TNTs) and exploits this route to spread to uninfected cells. In cellulo correlative fluorescence and cryo–electron tomography reveal that SARS-CoV-2 is associated with TNTs between permissive cells. Furthermore, multiple vesicular structures such as double-membrane vesicles, sites of viral replication, are observed inside TNTs between permissive and nonpermissive cells. Our data highlight a previously unknown mechanism of SARS-CoV-2 spreading, likely used as a route to invade nonpermissive cells and potentiate infection in permissive cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Tunneling nanotubes provide a route for SARS-CoV-2 spreading

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In addition to the above-mentioned main categories, the presence of other cell structural units (i.e., focal adhesion, lamellipodium, ruffle, membrane raft) suggests a role of S1 in the interaction with the actin cytoskeleton dynamics at the plasma membrane as well as the interaction with structure binding extracellular matrix (ECM) ( Figure 2C ). All these peripheral cell processes are well known to have a pivotal role in virus propagation mechanisms into host cells ( Kloc et al, 2022 ) and are much more representative in Caco-2, than in the other cell lines under investigation.…”

Section: Resultsmentioning

confidence: 99%

Spike S1 domain interactome in non-pulmonary systems: A role beyond the receptor recognition

Iacobucci

Monaco

Canè

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which, since 2019 in China, has rapidly become a worldwide pandemic. The aggressiveness and global spread were enhanced by the many SARS-CoV-2 variants that have been isolated up to now. These mutations affect mostly the viral glycoprotein Spike (S), the capsid protein mainly involved in the early stages of viral entry processes, through the recognition of specific receptors on the host cell surface. In particular, the subunit S1 of the Spike glycoprotein contains the Receptor Binding Domain (RBD) and it is responsible for the interaction with the angiotensin-converting enzyme 2 (ACE2). Although ACE2 is the primary Spike host receptor currently studied, it has been demonstrated that SARS-CoV-2 is also able to infect cells expressing low levels of ACE2, indicating that the virus may have alternative receptors on the host cells. The identification of the alternative receptors can better elucidate the pathogenicity and the tropism of SARS-CoV-2. Therefore, we investigated the Spike S1 interactomes, starting from host membrane proteins of non-pulmonary cell lines, such as human kidney (HK-2), normal colon (NCM460D), and colorectal adenocarcinoma (Caco-2). We employed an affinity purification-mass spectrometry (AP-MS) to pull down, from the membrane protein extracts of all cell lines, the protein partners of the recombinant form of the Spike S1 domain. The purified interactors were identified by a shotgun proteomics approach. The lists of S1 potential interacting proteins were then clusterized according to cellular localization, biological processes, and pathways, highlighting new possible S1 intracellular functions, crucial not only for the entrance mechanisms but also for viral replication and propagation processes.

show abstract

“… Ensp11nsp14nsp15nsp16ORF7bS 2 Actin, cytoplasmic 1 (ACTB) Fungal infection, such as Candida is already known to affect cellular actin during the study of interactions between Candida and HEp2 cells [70] . Candida is also known to stimulate actin polymerization by C. albicans phagosomes which help them to escape growing yeast from macrophages [27] SARS-CoV2 interaction with the actin cytoskeleton and related functions is important for viral pathogenicity, infection and other necessary functions [38] . Ensp4ORF10ORF7bORF8 3 Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) It is identified as an important adhesion factor for fungal host interaction during the study of Penicillium marneffei and Candida albicans [44] GAPDH is suggested to play various roles in responses against SARS-CoV2 infection and therefore proposed as an inhibitor for coronaviruses through IFN gamma and NO pathways [8] MEnsp13nsp4nsp6ORF10ORF8S 4 Tumor suppressor p53 (TP53) p53-like proteins from C. albicans are essential for virulence, hyphal growth, and antifungal resistance [33] .…”

Section: Resultsmentioning

confidence: 99%