Hepatitis C virus and host cell nuclear transport machinery: a clandestine affair

Bonamassa, Barbara; Ciccarese, Francesco; Antonio, Veronica Di; Contarini, Andrea; Palù, Giorgio; Alvisi, Gualtiero

doi:10.3389/fmicb.2015.00619

Cited by 12 publications

(13 citation statements)

References 77 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings were independently supported by results from the literature. HCV proteins, NS5B and NS3, were shown to move into the nucleus (22). The viral protein core was shown to interact with the transcription factor RXRA and could influence the transcription of infected cells (23).…”

Section: Introductionmentioning

confidence: 99%

“…The viral protein core was shown to interact with the transcription factor RXRA and could influence the transcription of infected cells (23). We anticipated that the invasion of viral proteins into the nucleus might be important during the chronic phase of infection and therefore may influence the pathogenic fate of the infected cell (22,24). Hence, we used HCV replicon cells that constitutively harbor HCV replicon RNA and thereby mimic a chronic HCV infection as our model system (25).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Nondimensional Model Reveals Alterations in Nuclear Mechanics upon Hepatitis C Virus Replication

Balakrishnan

Mathad

Sharma

et al. 2019

Biophysical Journal

View full text Add to dashboard Cite

Morphology of the nucleus is an important regulator of gene expression. Nuclear morphology is in turn a function of the forces acting on it and the mechanical properties of the nuclear envelope. Here, we present a two-parameter, nondimensional mechanical model of the nucleus that reveals a relationship among nuclear shape parameters, such as projected area, surface area, and volume. Our model fits the morphology of individual nuclei and predicts the ratio between forces and modulus in each nucleus. We analyzed the changes in nuclear morphology of liver cells due to hepatitis C virus (HCV) infection using this model. The model predicted a decrease in the elastic modulus of the nuclear envelope and an increase in the pre-tension in cortical actin as the causes for the change in nuclear morphology. These predictions were validated biomechanically by showing that liver cells expressing HCV proteins possessed enhanced cellular stiffness and reduced nuclear stiffness. Concomitantly, cells expressing HCV proteins showed downregulation of lamin-A,C and upregulation of b-actin, corroborating the predictions of the model. Our modeling assumptions are broadly applicable to adherent, monolayer cell cultures, making the model amenable to investigate changes in nuclear mechanics due to other stimuli by merely measuring nuclear morphology. Toward this, we present two techniques, graphical and numerical, to use our model for predicting physical changes in the nucleus.Huh7 and HCV replicon cells were seeded at 80% confluency in 35-mm dishes and allowed to grow for 24 h. Huh7 cells were treated with 6 mM Nondimensional Mechanical Nuclear Model

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Nondimensional Model Reveals Alterations in Nuclear Mechanics upon Hepatitis C Virus Replication

Balakrishnan

Mathad

Sharma

et al. 2019

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…The SUMO system has been shown to be also required for the replication of hepatitis C virus (HCV), the best characterized member of the Hepacivirus genus of the Flaviviridae family with several proteins containing functional NLSs and nuclear export signals (NESs) including the core, NS2, NS3, and NS5 proteins [90]. HCV infection upregulates SUMO1 expression, a host factor essential for HCV replication [91].…”

Section: Flaviviridaementioning

confidence: 99%

SUMO and Cytoplasmic RNA Viruses: From Enemies to Best Friends

Motiam

Vidal

Seoane

et al. 2020

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

SUMO is a ubiquitin-like protein that covalently binds to lysine residues of target proteins and regulates many biological processes such as protein subcellular localization or stability, transcription, DNA repair, innate immunity, or antiviral defense. SUMO has a critical role in the signaling pathway governing type I interferon (IFN) production, and among the SUMOylation substrates are many IFN-induced proteins. The overall effect of IFN is increasing global SUMOylation, pointing to SUMO as part of the antiviral stress response. Viral agents have developed different mechanisms to counteract the antiviral activities exerted by SUMO, and some viruses have evolved to exploit the host SUMOylation machinery to modify their own proteins. The exploitation of SUMO has been mainly linked to nuclear replicating viruses due to the predominant nuclear localization of SUMO proteins and enzymes involved in SUMOylation. However, SUMOylation of numerous viral proteins encoded by RNA viruses replicating at the cytoplasm has been lately described. Whether nuclear localization of these viral proteins is required for their SUMOylation is unclear. Here, we summarize the studies on exploitation of SUMOylation by cytoplasmic RNA viruses and discuss about the requirement for nuclear localization of their proteins. Keywords SUMO · RNA viruses · Interferon SUMO ConjugationSUMOylation consists in the covalent attachment of the small ubiquitin-like modifier (SUMO) proteins to specific lysine residues of a target protein. This conjugation is an enzymatic process that occurs in cascade. The precursor SUMO proteins are proteolytically processed to the

show abstract

“…NS5A negatively regulates interleukin (IL)‐8 gene by directly interacting with its promoter. NS5A is also known to increase the transcription of some negative regulators like lymphotoxin‐β . HCV core protein also has four potential NLS domains in the N‐terminal and two NES domains in the C‐terminal.…”

Section: Nucleus Is Not Left Untouched By the Cytoplasmic Virusmentioning

confidence: 99%

Hepatitis C virus: Enslavement of host factors

Sharma

Raheja

2017

IUBMB Life

View full text Add to dashboard Cite

Hepatitis C virus (HCV) has infected over 170 million people world-wide. This infection causes severe liver damage that can progress to hepatocellular carcinoma leading to death of the infected patients. Development of a cell culture model system for the study of HCV infection in the recent past has helped the researchers world-wide to understand the biology of this virus. Studies over the past decade have revealed the tricks played by the virus to sustain itself, for as long as 40 years, in the host setup without being eliminated by the immune system. Today we understand that the host organelles and different cellular proteins are affected during HCV infection. This cytoplasmic virus has all the cellular organelles at its disposal to successfully replicate, from ribosomes and intracellular membranous structures to the nucleus. It modulates these organelles at both the structural and the functional levels. The vast knowledge about the viral genome and viral proteins has also helped in the development of drugs against the virus. Despite the achieved success rate to cure the infected patients, we struggle to eliminate the cases of recurrence and the non-responders. Such cases might emerge owing to the property of the viral genome to accumulate mutations during its succeeding replication cycles which favours its survival. The current situation calls an urgent need for alternate therapeutic strategies to counter this major problem of human health. © 2017 IUBMB Life, 70(1):41-49, 2018.

show abstract

Hepatitis C virus and host cell nuclear transport machinery: a clandestine affair

Cited by 12 publications

References 77 publications

A Nondimensional Model Reveals Alterations in Nuclear Mechanics upon Hepatitis C Virus Replication

A Nondimensional Model Reveals Alterations in Nuclear Mechanics upon Hepatitis C Virus Replication

SUMO and Cytoplasmic RNA Viruses: From Enemies to Best Friends

Hepatitis C virus: Enslavement of host factors

Contact Info

Product

Resources

About