Calcium-signal facilitates herpes simplex virus type 1 nuclear transport through slingshot 1 and calpain-1 activation

Zheng, Kai; Xiang, Yangfei; Wang, Qiaoli; Jin, Fujun; Chen, Maoyun; Ma, Kaiqi; Ren, Zhe; Wang, Yifei

doi:10.1016/j.virusres.2014.03.016

Cited by 9 publications

(7 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They are capable of remodeling the cytoskeleton (Upla et al, 2008), which suggests that calpains may play a key role in vesicular trafficking and viral entry and intracellular migration. Furthermore, based on previous studies that reported an important role for calpain 1 in infection, intracellular trafficking and uncoating of echovirus 1, coxsackievirus, human immunodeficiency virus type 1, hepatitis C virus and herpes simplex virus type 1 (Upla et al, 2008;Bozym et al, 2010;Zheng et al, 2014), we focused on calpain 1 for further studies and found that inhibition of calpain 1 strongly suppressed viral replication in both MARC-145 cells and PAMs (Figure 7). The calpain 1 -CD163 interaction requires the SRCR5 domain, which is consistent with our data of LC-MS/MS.…”

Section: Discussionmentioning

confidence: 99%

CD163ΔSRCR5 MARC-145 Cells Resist PRRSV-2 Infection via Inhibiting Virus Uncoating, Which Requires the Interaction of CD163 With Calpain 1

Wei

Dong

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

Porcine alveolar macrophages without the CD163 SRCR5 domain are resistant to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, whether the deletion of CD163 SRCR5 in MARC-145 cells confers resistance to PRRSV and interaction of which of the host proteins with CD163 is involved in virus uncoating remain unclear. Here we deleted the SRCR5 domain of CD163 in MARC-145 cells using CRISPR/Cas9 to generate a CD163 SRCR5 MARC-145 cell line. The modification of CD163 had no impact on CD163 expression. CD163 SRCR5 cells were completely resistant to infection by PRRSV-2 strains Li11, CHR6, TJM, and VR2332. The modified cells showed no cytokine response to PRRSV-2 infection and maintained normal cell vitality comparable with the WT cells. The resistant phenotype of the cells was stably maintained through cell passages. There were no replication transcription complexes in the CD163 SRCR5 cells. SRCR5 deletion did not disturb the colocalization of CD163 and PRRSV-N in early endosomes (EE). However, the interaction of the viral proteins GP2a, GP3, or GP5 with CD163, which is involved in virus uncoating was affected. Furthermore, 77 CD163-binding cellular proteins affected by the SRCR5 deletion were identified by LC-MS/MS. Inhibition of calpain 1 trapped the virions in EE and forced then into late endosomes but did not block viral attachment and internalization, suggesting that calpain 1 is involved in the uncoating. Overall, CD163 SRCR5 MARC-145 cells are fully resistant to PRRSV-2 infection and calpain 1 is identified as a novel host protein that interacts with CD163 to facilitate PRRSV uncoating.

show abstract

Section: Discussionmentioning

confidence: 99%

CD163ΔSRCR5 MARC-145 Cells Resist PRRSV-2 Infection via Inhibiting Virus Uncoating, Which Requires the Interaction of CD163 With Calpain 1

Wei

Dong

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…On the other hand, taking into account the abundancy of calpains in cells and that their activity is mainly regulated by calcium concentration, calpains may play a role in multiple steps during the infection. In addition to enteroviruses, calpains have also been associated with other virus infections, such as influenza, herpesvirus, chikungunya, and other picornaviruses [45][46][47][48][49][50]. Particularly, processing of a viral protein by calpains has been shown with another RNA virus, Hepatitis C virus [51].…”

Section: Discussionmentioning

confidence: 99%

Host Cell Calpains Can Cleave Structural Proteins from the Enterovirus Polyprotein

Laajala

Hankaniemi

Määttä

et al. 2019

Viruses

View full text Add to dashboard Cite

Enteroviruses are small RNA viruses that cause diseases with various symptoms ranging from mild to severe. Enterovirus proteins are translated as a single polyprotein, which is cleaved by viral proteases to release capsid and nonstructural proteins. Here, we show that also cellular calpains have a potential role in the processing of the enteroviral polyprotein. Using purified calpains 1 and 2 in an in vitro assay, we show that addition of calpains leads to an increase in the release of VP1 and VP3 capsid proteins from P1 of enterovirus B species, detected by western blotting. This was prevented with a calpain inhibitor and was dependent on optimal calcium concentration, especially for calpain 2. In addition, calpain cleavage at the VP3-VP1 interface was supported by a competition assay using a peptide containing the VP3-VP1 cleavage site. Moreover, a mass spectrometry analysis showed that calpains can cleave this same peptide at the VP3-VP1 interface, the cutting site being two amino acids aside from 3C’s cutting site. Furthermore, we show that calpains cannot cleave between P1 and 2A. In conclusion, we show that cellular proteases, calpains, can cleave structural proteins from enterovirus polyprotein in vitro. Whether they assist polyprotein processing in infected cells remains to be shown.

show abstract

“…As will be discussed later, nuclear translocation of the Arp2/3 complex, nuclear F-actin polymerization, and the resultant perturbation of nuclear structure also play a critical role during viral assembly and egress (Ohkawa T, et al, 1999; Goley ED, et al, 2006). HSV-1 has also been shown to utilize actin for intracellular motility and nuclear localization in a process involving the cofilin phosphatase and activator, slingshot, and calcium-regulated protease, calpain (Zheng K, et al, 2014 a ). The siRNA knockdown of slingshot and calpain reduced viral infection and led to a perinuclear localization of the viral cores, whereas wild-type virus localized to the nucleus efficaciously.…”

Section: Actin and Nuclear Migrationmentioning

confidence: 99%

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

Spear

2014

Virol. Sin.

View full text Add to dashboard Cite

As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array of mechanisms for manipulating the actin cytoskeleton for efficacious infection. An ongoing chorus of research now indicates that the actin cytoskeleton is critical for viral replication at many stages of the viral life cycle, including binding, entry, nuclear localization, genomic transcription and reverse transcription, assembly, and egress/dissemination. Specifically, viruses subvert the force-generating and macromolecular scaffolding properties of the actin cytoskeleton to propel viral surfing, internalization, and migration within the cell. Additionally, viruses utilize the actin cytoskeleton to support and organize assembly sites, and eject budding virions for cell-to-cell transmission. It is the purpose of this review to provide an overview of current research, focusing on the various mechanisms and themes of virus-mediated actin modulation described therein.

show abstract

Calcium-signal facilitates herpes simplex virus type 1 nuclear transport through slingshot 1 and calpain-1 activation

Cited by 9 publications

References 28 publications

CD163ΔSRCR5 MARC-145 Cells Resist PRRSV-2 Infection via Inhibiting Virus Uncoating, Which Requires the Interaction of CD163 With Calpain 1

CD163ΔSRCR5 MARC-145 Cells Resist PRRSV-2 Infection via Inhibiting Virus Uncoating, Which Requires the Interaction of CD163 With Calpain 1

Host Cell Calpains Can Cleave Structural Proteins from the Enterovirus Polyprotein

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

Contact Info

Product

Resources

About