Viral exploitation of actin: force-generation and scaffolding functions in viral infection

Spear, Mark; Wu, Yuntao

doi:10.1007/s12250-014-3476-0

Cited by 30 publications

(32 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HIV binding, receptor clustering and intracellular transport of the viral genome toward the nucleus as well as to budding sites happens to necessitate functional interactions with the host actin cytoskeleton (Stolp and Fackler, 2011 ). It has been shown in CD4+ lymphocytes that suppression of cytoskeleton regulators (Arp2/3 and WAVE2) prevented HIV-1 infection diminishing its intracellular migration (Spear and Wu, 2014 ). Our data indicate that PARPi prevented HIV-1 from hijacking the cytoskeletal cell compartment, shown by complete blockage of F/G-actin transition by preventing the actin severing protein, cofilin, to become activated via attenuation of RhoA/Rac1 signaling (Figure 9 ).…”

Section: Discussionmentioning

confidence: 99%

The dual action of poly(ADP-ribose) polymerase -1 (PARP-1) inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity

et al. 2015

View full text Add to dashboard Cite

Multifactorial mechanisms comprising countless cellular factors and virus-encoded transactivators regulate the transcription of HIV-1 (HIV). Since poly(ADP-ribose) polymerase 1 (PARP-1) regulates numerous genes through its interaction with various transcription factors, inhibition of PARP-1 has surfaced recently as a powerful anti-inflammatory tool. We suggest a novel tactic to diminish HIV replication via PARP-1 inhibition in an in vitro model system, exploiting human primary monocyte-derived macrophages (MDM). PARP-1 inhibition was capable to lessen HIV replication in MDM by 60–80% after 7 days infection. Tat, tumor necrosis factor α (TNFα), and phorbol 12-myristate 13-acetate (PMA) are known triggers of the Long Terminal Repeat (LTR), which can switch virus replication. Tat overexpression in MDM transfected with an LTR reporter plasmid resulted in a 4.2-fold increase in LTR activation; PARP inhibition caused 70% reduction of LTR activity. LTR activity, which increased 3-fold after PMA or TNFα treatment, was reduced by PARP inhibition (by 85–95%). PARP inhibition in MDM exhibited 90% diminution in NFκB activity (known to mediate TNFα- and PMA-induced HIV LTR activation). Cytoskeleton rearrangements are important in effective HIV-1 infection. PARP inactivation reduced actin cytoskeleton rearrangements by affecting Rho GTPase machinery. These discoveries suggest that inactivation of PARP suppresses HIV replication in MDM by via attenuation of LTR activation, NFκB suppression and its effects on the cytoskeleton. PARP appears to be essential for HIV replication and its inhibition may provide an effective approach to management of HIV infection.

show abstract

Section: Discussionmentioning

confidence: 99%

The dual action of poly(ADP-ribose) polymerase -1 (PARP-1) inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Although each protein has been identified and characterized singularly, this growing trend may indicate broader relationships between cytoskeletal functions and innate immune regulation and activity. Consistent with this view, bacteria and viruses both modulate actin polymerization as central components of infection and replication [ 133 , 134 ]. Furthermore, perturbation of the actin cytoskeleton activates cytoskeleton-associated PRRs [ 135 , 136 , 137 ].…”

Section: Cytoskeletal Interactions As a Component Of The Innate Immentioning

confidence: 88%

“…Bacteria utilize actin polymerization for many purposes such as forming pedestals to mediate attachment and invasion, generating actin tails for disseminating throughout the cytosol, or to mediate intercellular spread [ 133 ]. Viruses remodel actin for almost every step of replication including invasion, migration to the nucleus, assembly, exocytosis, and budding [ 134 ]. These are all conserved and universal activities that are unlikely to be lost through adaptation, and therefore make pathogen-induced cytoskeletal perturbations good targets for innate immune activation.…”

Section: A Network Of Innate Immune Mediators Link Pathogen Sensinmentioning

confidence: 99%

The Roles of RNase-L in Antimicrobial Immunity and the Cytoskeleton-Associated Innate Response

Ezelle

Malathi

Hassel

2016

IJMS

View full text Add to dashboard Cite

The interferon (IFN)-regulated endoribonuclease RNase-L is involved in multiple aspects of the antimicrobial innate immune response. It is the terminal component of an RNA cleavage pathway in which dsRNA induces the production of RNase-L-activating 2-5A by the 2′-5′-oligoadenylate synthetase. The active nuclease then cleaves ssRNAs, both cellular and viral, leading to downregulation of their expression and the generation of small RNAs capable of activating retinoic acid-inducible gene-I (RIG-I)-like receptors or the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome. This leads to IFNβ expression and IL-1β activation respectively, in addition to broader effects on immune cell function. RNase-L is also one of a growing number of innate immune components that interact with the cell cytoskeleton. It can bind to several cytoskeletal proteins, including filamin A, an actin-binding protein that collaborates with RNase-L to maintain the cellular barrier to viral entry. This antiviral activity is independent of catalytic function, a unique mechanism for RNase-L. We also describe here the interaction of RNase-L with the E3 ubiquitin ligase and scaffolding protein, ligand of nump protein X (LNX), a regulator of tight junction proteins. In order to better understand the significance and context of these novel binding partners in the antimicrobial response, other innate immune protein interactions with the cytoskeleton are also discussed.

show abstract

“…Furthermore, exposure to HSV-1 induces increased formation of filopodia, enhancing chances of viral attachment and providing a mechanism for targeted delivery of viral particles to the cell body for entry [7]. Viral surfing has also been observed for vaccinia virus, HPV type 16, HCV and HIV [9], suggesting that manipulation of the actin cytoskeleton may be a general mechanism of virus targeting and entry to the cell body.…”

Section: Viral Attachment To Cellsmentioning

confidence: 99%

Cell Entry Mechanisms of HSV: What we have Learned in Recent Years

2015

View full text Add to dashboard Cite

HSV type-1 and -2 are widespread pathogens producing lifelong infection with multiple sequelae, including oral, ocular and genital disease. The process of herpesvirus entry is a highly complex process involving numerous viral and cellular factors. Entry begins with attachment of virus to the cell surface followed by interactions between viral glycoproteins and cellular receptors to facilitate capsid penetration. The nucleocapsid is then transported along microtubules to the nuclear membrane, where viral DNA is released for replication in the nucleus. The work reviewed here comprises the most recent advancements in our understanding of the mechanism involved in the herpesvirus entry process.

show abstract

Viral exploitation of actin: force-generation and scaffolding functions in viral infection

Cited by 30 publications

References 67 publications

The dual action of poly(ADP-ribose) polymerase -1 (PARP-1) inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity

The dual action of poly(ADP-ribose) polymerase -1 (PARP-1) inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity

The Roles of RNase-L in Antimicrobial Immunity and the Cytoskeleton-Associated Innate Response

Cell Entry Mechanisms of HSV: What we have Learned in Recent Years

Contact Info

Product

Resources

About