Equine Alphaherpesviruses Require Activation of the Small GTPases Rac1 and Cdc42 for Intracellular Transport

Kolyvushko, Oleksandr; Kelch, Maximilian A.; Osterrieder, Nikolaus; Azab, Walid

doi:10.3390/microorganisms8071013

Cited by 14 publications

(7 citation statements)

References 63 publications

(95 reference statements)

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“…In the horse, a few studies about α4β1 integrin are available [26][27][28][29][30][31][32], and are related to its presence on leukocytes [26,29] and endometrial epithelial cells [27,28] or equine herpesvirus 1 infection mechanism [30][31][32]. Integrins represent one of the most important families of cell adhesion receptors that mediate cell-cell and cell-ECM interactions.…”

Section: Discussionmentioning

confidence: 99%

Peptide Mediated Adhesion to Beta-Lactam Ring of Equine Mesenchymal Stem Cells: A Pilot Study

Merlo

Baldassarro

Flagelli

et al. 2022

Animals

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Regenerative medicine applied to skin lesions is a field in constant improvement. The use of biomaterials with integrin agonists could promote cell adhesion increasing tissue repair processes. The aim of this pilot study was to analyze the effect of an α4β1 integrin agonist on cell adhesion of equine adipose tissue (AT) and Wharton’s jelly (WJ) derived MSCs and to investigate their adhesion ability to GM18 incorporated poly L-lactic acid (PLLA) scaffolds. Adhesion assays were performed after culturing AT- and WJ-MSCs with GM18 coating or soluble GM18. Cell adhesion on GM18 containing PLLA scaffolds after 20 min co-incubation was assessed by HCS. Soluble GM18 affects the adhesion of equine AT- and WJ-MSCs, even if its effect is variable between donors. Adhesion to PLLA scaffolds containing GM18 is not significantly influenced by GM18 for AT-MSCs after 20 min or 24 h of culture and for WJ-MSCs after 20 min, but increased cell adhesion by 15% GM18 after 24 h. In conclusion, the α4β1 integrin agonist GM18 affects equine AT- and WJ-MSCs adhesion ability with a donor-related variability. These preliminary results represent a first step in the study of equine MSCs adhesion to PLLA scaffolds containing GM18, suggesting that WJ-MSCs might be more suitable than AT-MSCs. However, the results need to be confirmed by increasing the number of samples before drawing definite conclusions.

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Section: Discussionmentioning

confidence: 99%

Peptide Mediated Adhesion to Beta-Lactam Ring of Equine Mesenchymal Stem Cells: A Pilot Study

Merlo

Baldassarro

Flagelli

et al. 2022

Animals

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“…We investigated Cdc42 GTPase, a well-studied signaling protein that regulates filopodia formation and actin rearrangement [23,24]. Cdc42 plays a role in the infectious process for several viruses, including HIV-1, HSV-1, EHV, EBV, HHV-8, strains of VACV, DEV-2, and RSV [25][26][27][28][29][30]. Using a PAK-PBD pulldown assay for active Cdc42, we demonstrate that there is an increase in GTP bound Cdc42 after 15 min of virus addition in HaCaT cells.…”

Section: Discussionmentioning

confidence: 99%

The Process of Filopodia Induction during HPV Infection

Biondo¹,

Meneses²

2022

Viruses

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Human Papillomavirus 16 (HPV16) infects mucosal and epithelial cells and has been identified as a high-risk HPV type that is an etiologic agent of human cancers. The initial infectious process, i.e., the binding of the virus particle and its entry into the host cell, has been studied extensively, although it is not fully understood. There is still a gap in understanding the steps by which the virus is able to cross the plasma membrane after receptor binding. In this study, we demonstrate that after HPV16 comes into contact with a plasma membrane receptor, there are cytoskeletal changes resulting in an increase of filopodia numbers. This increase in filopodia numbers was transient and was maintained during the first two hours after virus addition. Our data show that there is a statistically significant increase in infection when filopodia numbers are increased by the addition of drug and virus simultaneously, and a decrease in virus infection when filopodia formation is inhibited. We describe that HPV16 binding results in the activation of Cdc42 GTPase that in turn results in an increase in filopodia. siRNA directed at Cdc42 GTPase resulted in a statistically significant reduction of infection and a corresponding lack of filopodia induction.

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“…Previous studies have shown that Cdc42 inhibitor ML141 does not block virus entry, but rather inhibits virus transport to the nucleus of α-herpesvirus equine herpesvirus type 1. 54 Additionally, studies have shown that B-Raf V600E inhibitors can interact with Ras-GTP. 55 This finding suggests that RAF265 targets Cdc42 via a Ras-mediated interaction, which prevents the nuclear import of HSV-1.…”

Section: Raf265 Presented Relatively Broad Antiviral Activitymentioning

confidence: 99%

Small molecule RAF265 as an antiviral therapy acts against HSV‐1 by regulating cytoskeleton rearrangement and cellular translation machinery

Chi

Wang

et al. 2022

Journal of Medical Virology

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Host‐targeting antivirals (HTAs) have received increasing attention for their potential as broad‐spectrum antivirals that pose relatively low risk of developing drug resistance. The repurposing of pharmaceutical drugs for use as antivirals is emerging as a cost‐ and time‐ efficient approach to developing HTAs for the treatment of a variety of viral infections. In this study, we used a virus titer method to screen 30 small molecules for antiviral activity against Herpes simplex virus‐1 (HSV‐1). We found that the small molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of B‐RAF V600E, reduced viral loads of HSV‐1 by 4 orders of magnitude in Vero cells and reduced virus proliferation in vivo. RAF265 mediated cytoskeleton rearrangement and targeted the host cell's translation machinery, which suggests that the antiviral activity of RAF265 may be attributed to a dual inhibition strategy. This study offers a starting point for further advances toward clinical development of antivirals against HSV‐1.

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Equine Alphaherpesviruses Require Activation of the Small GTPases Rac1 and Cdc42 for Intracellular Transport

Cited by 14 publications

References 63 publications

Peptide Mediated Adhesion to Beta-Lactam Ring of Equine Mesenchymal Stem Cells: A Pilot Study

Peptide Mediated Adhesion to Beta-Lactam Ring of Equine Mesenchymal Stem Cells: A Pilot Study

The Process of Filopodia Induction during HPV Infection

Small molecule RAF265 as an antiviral therapy acts against HSV‐1 by regulating cytoskeleton rearrangement and cellular translation machinery

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