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

The actin cytoskeleton and actin-dependent molecular and cellular events are responsible for the organization of eukaryotic cells and their functions. Viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), depend on host cell organelles and molecular components for cell entry and propagation. Thus, it is not surprising that they also interact at many levels with the actin cytoskeleton of the host. There have been many studies on how different viruses reconfigure and manipulate the actin cytoskeleton of the host during successive steps of their life cycle. However, we know relatively little about the interactions of SARS-CoV-2 with the actin cytoskeleton. Here, we describe how the actin cytoskeleton is involved in the strategies used by different viruses for entry, assembly, and egress from the host cell. We emphasize what is known and unknown about SARS-CoV-2 in this regard. This review should encourage further investigation of the interactions of SARS-CoV-2 with cellular components, which will eventually be helpful for developing novel antiviral therapies for mitigating the severity of COVID-19.

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

The actin cytoskeleton and actin-dependent molecular and cellular events are responsible for the organization of eukaryotic cells and their functions. Viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), depend on host cell organelles and molecular components for cell entry and propagation. Thus, it is not surprising that they also interact at many levels with the actin cytoskeleton of the host. There have been many studies on how different viruses reconfigure and manipulate the actin cytoskeleton of the host during successive steps of their life cycle. However, we know relatively little about the interactions of SARS-CoV-2 with the actin cytoskeleton. Here, we describe how the actin cytoskeleton is involved in the strategies used by different viruses for entry, assembly, and egress from the host cell. We emphasize what is known and unknown about SARS-CoV-2 in this regard. This review should encourage further investigation of the interactions of SARS-CoV-2 with cellular components, which will eventually be helpful for developing novel antiviral therapies for mitigating the severity of COVID-19.

Reciprocal interactions between mesenchymal stem cells and macrophages.

Mesenchymal stem cells (MSCs) are used as therapeutic agents for the treatment of a wide spectrum of diseases, as well as for the regeneration and healing of burns and wounds. MSCs have an immunomodulatory effect and influence the phenotype and functions of immune cells, including macrophages, which in turn prime and license the MSCs. We discuss the new findings on the feedback loop between MSCs and macrophages and its consequences on the outcome of MSC therapies.

Exaptation of Retroviral Syncytin for Development of Syncytialized Placenta, Its Limited Homology to the SARS-CoV-2 Spike Protein and Arguments against Disturbing Narrative in the Context of COVID-19 Vaccination.

Human placenta formation relies on the interaction between fused trophoblast cells of the embryo with uterine endometrium. The fusion between trophoblast cells, first into cytotrophoblast and then into syncytiotrophoblast, is facilitated by the fusogenic protein syncytin. Syncytin derives from an envelope glycoprotein (ENV) of retroviral origin. In exogenous retroviruses, the envelope glycoproteins coded by env genes allow fusion of the viral envelope with the host cell membrane and entry of the virus into a host cell. During mammalian evolution, the env genes have been repeatedly, and independently, captured by various mammalian species to facilitate the formation of the placenta. Such a shift in the function of a gene, or a trait, for a different purpose during evolution is called an exaptation (co-option). We discuss the structure and origin of the placenta, the fusogenic and non-fusogenic functions of syncytin, and the mechanism of cell fusion. We also comment on an alleged danger of the COVID-19 vaccine based on the presupposed similarity between syncytin and the SARS-CoV-2 spike protein.

Effects of vitamin D on macrophages and myeloid-derived suppressor cells (MDSCs) hyperinflammatory response in the lungs of COVID-19 patients.

Vitamin D regulates homeostasis, anti-microbial response, and inflammation. The vitamin D receptors are expressed in the macrophages and other immune cells, regulating the transcription of many different genes, including those coding the anti-microbial peptides. One of the most severe complications of the SARS-CoV-2 infection is the acute respiratory distress syndrome (ARDS) caused by the hyperinflammatory response (commonly called cytokine storm) of the lung macrophages. Studies showed that Vitamin D deficiency increases the severity of the ARDS in COVID-19 infection. We discuss here how the vitamin D supplementation may influence macrophage and myeloid-derived suppressor cells (MDSCs) inflammatory response, subdue the hyperinflammatory response, and lessen the ARDS in COVID-19 patients.

Macrophages in diabetes mellitus (DM) and COVID-19: do they trigger DM?

Diabetes mellitus (DM) augments the risk of hospitalization and mortality resulting from viral, bacterial, or fungal pathogen infection. This has been also true for the past SARS and MERS, and current SARS-CoV-2 coronavirus epidemics. Clinical data indicate that SARS-CoV-2 infection triggers a severe course of COVID-19 more frequently in diabetic than non-diabetic patients. Here we overview the cellular and molecular mechanisms associated with this phenomenon. We focus on alterations in the immune cells, especially monocytes and macrophages, involved in innate immune response and inflammatory processes, which differ in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). We also describe the DM-related changes in the monocyte/macrophages functions, how they could lead to the severe outcome of SARS-CoV-2 infection, and importantly, if and how they could initiate DM in DM-susceptible patients.

The multiple sclerosis (MS) drugs as a potential treatment of ARDS in COVID-19 patients.

We encourage studies on the effectiveness of multiple sclerosis drugs for the treatment of ARDS in COVID-19 infection. These drugs, through the inhibition of the RhoA/actin-dependent expression of virus receptors in the macrophages and macrophage recruitment to the lungs, have the potential to inhibit cytokine storm of lung macrophages, reduce or eliminate ARDS and improve the outcome of COVID-19 infection.

Development of child immunity in the context of COVID-19 pandemic.

Children, because of having an immature immune system, are usually more prone than the adults to the microbial infections and have more severe symptoms, which is especially true for the newborns, and very young children. However, the review of clinical data from the current COVID-19 pandemic indicates otherwise. We discuss here what are the main features and components of children's immune system, the role of maternal transmission of immunity, and what are the possible explanations for the seemingly lower infection rate and severity of COVI-19 in children.

How nicotine can inhibit cytokine storm in the lungs and prevent or lessen the severity of COVID-19 infection?

Statistical surveys of COVID-19 patients indicate, against all common logic, that people who smoke are less prone to the infection and/or exhibit less severe respiratory symptoms than non-smokers. This suggests that nicotine may have some preventive or modulatory effect on the inflammatory response in the lungs. Because it is known that the response to, and resolution of the SARS-CoV-2 infection depends mainly on the lung macrophages, we discuss the recent scientific findings, which may explain why and how nicotine may modulate lung macrophage response during COVID-19 infection.