SCIENCE@home

Phospho-activated non-muscle myosin IIA heavy chain supports different mechanisms of virus uptake

Natalia Ansin,Kathia Guardado,M. Ponce,María Paz García,Camila Ladra,Irene Ferreiro,G. Moratorio,Nicolás Sarute

Published 2025 in Journal of Virology

ABSTRACT

ABSTRACT Limiting virus entry is crucial to prevent infection, since this step of the virus life cycle is a major determinant of cellular tropism, host range, and pathogenesis. We recently showed that the transmembrane protein signal regulatory protein alpha (SIRPA), a negative regulator of F-actin-dependent phagocytosis, limits endocytosis of enveloped RNA viruses from unrelated families. Mechanistically, surface engagement of SIRPA recruits the SH2 domain-containing protein tyrosine phosphatases (SHP)-1 and -2, initiating a signaling cascade that dephosphorylates different pro-phagocytic proteins, including the heavy chain (MYH9) of the molecular motor non-muscle myosin IIA (NM-IIA), to ultimately suppress phagocytosis. Here, we analyzed whether MYH9 would enhance viral infection, as it does phagocytic engulfment, and how its activity in infection is regulated. We found that MYH9 expression increases the infection of viruses exploiting different endocytic pathways/mechanisms to enter cells, including flavivirus, arenavirus, rhabdovirus, and togavirus, in human and mouse cells. Furthermore, we demonstrated that MYH9 is actively translocated to the plasma membrane upon viral infection to support post-binding steps of entry, and that phosphorylation of two key tyrosine residues in its head and tail domains is essential for its function in viral infection. By using small molecule inhibitors and MYH9 knockdown cells, we suggest that members of the Src family kinases may phosphorylate/activate MYH9 to support virus entry. IMPORTANCE Viral infections represent a major threat to global public health and pose a huge social and economic cost; thus, a better understanding of how cell-intrinsic factors modulate the outcome of infection is of great importance to better understand virus–host interactions and to our ability to develop prophylactic measures and therapeutics. In this work, we show that MYH9 is a broad proviral host factor that enhances entry of divergent families of human pathogenic RNA viruses, which exploit different endocytic pathways to infect cells. By determining that virus infection triggers the phosphorylation of MYH9 in two tyrosine residues essential for its proviral activity, and the family of non-receptor tyrosine kinases involved in this process, we may also provide new cellular targets to develop antiviral therapies. Viral infections represent a major threat to global public health and pose a huge social and economic cost; thus, a better understanding of how cell-intrinsic factors modulate the outcome of infection is of great importance to better understand virus–host interactions and to our ability to develop prophylactic measures and therapeutics. In this work, we show that MYH9 is a broad proviral host factor that enhances entry of divergent families of human pathogenic RNA viruses, which exploit different endocytic pathways to infect cells. By determining that virus infection triggers the phosphorylation of MYH9 in two tyrosine residues essential for its proviral activity, and the family of non-receptor tyrosine kinases involved in this process, we may also provide new cellular targets to develop antiviral therapies.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-52 of 52 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1