scholarly journals Role of Endoplasmic Reticulum-Associated Proteins in Flavivirus Replication and Assembly Complexes

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 148 ◽  
Author(s):  
Hussin A. Rothan ◽  
Mukesh Kumar
Keyword(s):  
Endoplasmic Reticulum ◽  
Viral Proteins ◽  
Host Cells ◽  
Host Proteins ◽  
Multiprotein Complexes ◽  
Genome Wide ◽  
Associated Proteins ◽  
Cytoplasmic Side ◽  
Er Membrane

Flavivirus replication in host cells requires the formation of replication and assembly complexes on the cytoplasmic side of the endoplasmic reticulum (ER) membrane. These complexes consist of an ER membrane, viral proteins, and host proteins. Genome-wide investigations have identified a number of ER multiprotein complexes as vital factors for flavivirus replication. The detailed mechanisms of the role of ER complexes in flavivirus replication are still largely elusive. This review highlights the fact that the ER multiprotein complexes are crucial for the formation of flavivirus replication and assembly complexes, and the ER complexes could be considered as a target for developing successful broad-spectrum anti-flavivirus drugs.

scholarly journals A novel putative microtubule-associated protein is involved in arbuscule development during arbuscular mycorrhiza formation

2021 ◽  
Author(s):  
Tania Ho-Plágaro ◽  
Raúl Huertas ◽  
María I Tamayo-Navarrete ◽  
Elison Blancaflor ◽  
Nuria Gavara ◽  
...  
Keyword(s):  
Plant Root ◽  
Arbuscular Mycorrhizal ◽  
Host Cells ◽  
Root Cells ◽  
Filament Dynamics ◽  
Fungal Structure ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Mycorrhizal Development

Abstract The formation of arbuscular mycorrhizal (AM) symbiosis requires plant root host cells to undergo major structural and functional reprogramming in order to house the highly branched AM fungal structure for the reciprocal exchange of nutrients. These morphological modifications are associated with cytoskeleton remodelling. However, molecular bases and the role of microtubules (MTs) and actin filament dynamics during AM formation are largely unknown. In this study, the tomato tsb gene, belonging to a Solanaceae group of genes encoding MT-associated proteins for pollen development, was found to be highly expressed in root cells containing arbuscules. At earlier stages of mycorrhizal development, tsb overexpression enhanced the formation of highly developed and transcriptionally active arbuscules, while tsb silencing hampers the formation of mature arbuscules and represses arbuscule functionality. However, at later stages of mycorrhizal colonization, tsb OE roots accumulate fully developed transcriptionally inactive arbuscules, suggesting that the collapse and turnover of arbuscules might be impaired by TSB accumulation. Imaging analysis of the MT cytoskeleton in cortex root cells overexpressing tsb revealed that TSB is involved in MT-bundling. Taken together, our results provide unprecedented insights into the role of novel MT-associated protein in MT rearrangements throughout the different stages of the arbuscule life cycle.

scholarly journals Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis

2020 ◽  
Vol 22 (1) ◽  
pp. 323
Author(s):  
Ramesh Kumar ◽  
Divya Mehta ◽  
Nimisha Mishra ◽  
Debasis Nayak ◽  
Sujatha Sunil
Keyword(s):  
Rna Virus ◽  
Viral Proteins ◽  
Post Translational Modification ◽  
Host Proteins ◽  
Viral Protein Synthesis ◽  
Post Translational Modifications ◽  
Small Proteins ◽  
Cellular Machinery ◽  
Chemical Groups

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins’ functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

scholarly journals Atlastin Endoplasmic Reticulum-Shaping Proteins Facilitate Zika Virus Replication

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Blandine Monel ◽  
Maaran Michael Rajah ◽  
Mohamed Lamine Hafirassou ◽  
Samy Sid Ahmed ◽  
Julien Burlaud-Gaillard ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Viral Replication ◽  
Zika Virus ◽  
Antiviral Treatment ◽  
Viral Proteins ◽  
Neurological Complications ◽  
Cytopathic Effects ◽  
Replication Sites ◽  
Infected Cells ◽  
Er Membrane

ABSTRACT The endoplasmic reticulum (ER) is the site for Zika virus (ZIKV) replication and is central to the cytopathic effects observed in infected cells. ZIKV induces the formation of ER-derived large cytoplasmic vacuoles followed by “implosive” cell death. Little is known about the nature of the ER factors that regulate flavivirus replication. Atlastins (ATL1, -2, and -3) are dynamin-related GTPases that control the structure and the dynamics of the ER membrane. We show here that ZIKV replication is significantly decreased in the absence of ATL proteins. The appearance of infected cells is delayed, the levels of intracellular viral proteins and released virus are reduced, and the cytopathic effects are strongly impaired. We further show that ATL3 is recruited to viral replication sites and interacts with the nonstructural viral proteins NS2A and NS2B3. Thus, proteins that shape and maintain the ER tubular network ensure efficient ZIKV replication. IMPORTANCE Zika virus (ZIKV) is an emerging virus associated with Guillain-Barré syndrome, and fetal microcephaly as well as other neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We found that endoplasmic reticulum (ER)-shaping atlastin proteins (ATL1, -2, and -3), which induce ER membrane fusion, facilitate ZIKV replication. We show that ATL3 is recruited to the viral replication site and colocalize with the viral proteins NS2A and NS2B3. The results provide insights into host factors used by ZIKV to enhance its replication.

scholarly journals Hsp70 Negatively Controls Rotavirus Protein Bioavailability in Caco-2 Cells Infected by the Rotavirus RF Strain

2006 ◽  
Vol 81 (3) ◽  
pp. 1297-1304 ◽  
Author(s):  
Alexis H. Broquet ◽  
Christelle Lenoir ◽  
Agnès Gardet ◽  
Catherine Sapin ◽  
Serge Chwetzoff ◽  
...  
Keyword(s):  
Viral Infection ◽  
Proteasome Inhibitors ◽  
Virus Production ◽  
Viral Proteins ◽  
Host Cells ◽  
Progeny Virus ◽  
Virus Protein ◽  
Interfering Rna ◽  
Hsp70 Induction

ABSTRACT Previous studies demonstrated that the induction of the heat shock protein Hsp70 in response to viral infection is highly specific and differs from one cell to another and for a given virus type. However, no clear consensus exists so far to explain the likely reasons for Hsp70 induction within host cells during viral infection. We show here that upon rotavirus infection of intestinal cells, Hsp70 is indeed rapidly, specifically, and transiently induced. Using small interfering RNA-Hsp70-transfected Caco-2 cells, we observed that Hsp70 silencing was associated with an increased virus protein level and enhanced progeny virus production. Upon Hsp70 silencing, we observed that the ubiquitination of the main rotavirus structural proteins was strongly reduced. In addition, the use of proteasome inhibitors in infected Caco-2 cells was shown to induce an accumulation of structural viral proteins. Together, these results are consistent with a role of Hsp70 in the control of the bioavailability of viral proteins within cells for virus morphogenesis.

scholarly journals HRDGene Dependence of Endoplasmic Reticulum-associated Degradation

2000 ◽  
Vol 11 (5) ◽  
pp. 1697-1708 ◽  
Author(s):  
Sharon Wilhovsky ◽  
Richard Gardner ◽  
Randolph Hampton
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Protein Degradation ◽  
Degradation Pathway ◽  
Encoded Proteins ◽  
Absolute Dependence ◽  
Coa Reductase ◽  
Ubiquitin Conjugating Enzymes ◽  
Er Membrane

Work from several laboratories has indicated that many different proteins are subject to endoplasmic reticulum (ER) degradation by a common ER-associated machinery. This machinery includes ER membrane proteins Hrd1p/Der3p and Hrd3p and the ER-associated ubiquitin-conjugating enzymes Ubc7p and Ubc6p. The wide variety of substrates for this degradation pathway has led to the reasonable hypothesis that the HRD (Hmg CoA reductase degradation) gene-encoded proteins are generally involved in ER protein degradation in eukaryotes. We have tested this model by directly comparing the HRD dependency of the ER-associated degradation for various ER membrane proteins. Our data indicated that the role of HRD genes in protein degradation, even in this highly defined subset of proteins, can vary from absolute dependence to complete independence. Thus, ER-associated degradation can occur by mechanisms that do not involve Hrd1p or Hrd3p, despite their apparently broad envelope of substrates. These data favor models in which the HRD gene-encoded proteins function as specificity factors, such as ubiquitin ligases, rather than as factors involved in common aspects of ER degradation.

scholarly journals SGTA-Dependent Regulation of Hsc70 Promotes Cytosol Entry of Simian Virus 40 from the Endoplasmic Reticulum

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Allison Dupzyk ◽  
Jeffrey M. Williams ◽  
Parikshit Bagchi ◽  
Takamasa Inoue ◽  
Billy Tsai
Keyword(s):  
Endoplasmic Reticulum ◽  
Biological Membrane ◽  
Critical Role ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Membrane Penetration ◽  
Critical Function ◽  
Nonenveloped Virus ◽  
Er Membrane

ABSTRACT Membrane penetration by nonenveloped viruses remains enigmatic. In the case of the nonenveloped polyomavirus simian virus 40 (SV40), the virus penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol and then traffics to the nucleus to cause infection. We previously demonstrated that the cytosolic Hsc70-SGTA-Hsp105 complex is tethered to the ER membrane, where Hsp105 and SGTA facilitate the extraction of SV40 from the ER and transport of the virus into the cytosol. We now find that Hsc70 also ejects SV40 from the ER into the cytosol in a step regulated by SGTA. Although SGTA's N-terminal domain, which mediates homodimerization and recruits cellular adaptors, is dispensable during ER-to-cytosol transport of SV40, this domain appears to exert an unexpected post-ER membrane translocation function during SV40 entry. Our study thus establishes a critical function of Hsc70 within the Hsc70-SGTA-Hsp105 complex in promoting SV40 ER-to-cytosol membrane penetration and unveils a role of SGTA in controlling this step. IMPORTANCE How a nonenveloped virus transports across a biological membrane to cause infection remains mysterious. One enigmatic step is whether host cytosolic components are co-opted to transport the viral particle into the cytosol. During ER-to-cytosol membrane transport of the nonenveloped polyomavirus SV40, a decisive infection step, a cytosolic complex composed of Hsc70-SGTA-Hsp105 was previously shown to associate with the ER membrane. SGTA and Hsp105 have been shown to extract SV40 from the ER and transport the virus into the cytosol. We demonstrate here a critical role of Hsc70 in SV40 ER-to-cytosol penetration and reveal how SGTA controls Hsc70 to impact this process.

scholarly journals HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

2016 ◽  
Vol 80 (3) ◽  
pp. 679-731 ◽  
Author(s):  
Guangdi Li ◽  
Erik De Clercq
Keyword(s):  
Life Cycle ◽  
Viral Entry ◽  
Large Body ◽  
Viral Proteins ◽  
Host Cells ◽  
Comprehensive Overview ◽  
Genome Wide ◽  
A Genome ◽  
Glycoprotein Gp120 ◽  
Physical Interactions

SUMMARYThe HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle.

scholarly journals Uncovering potential host proteins and pathways that may interact with eukaryotic short linear motifs in viral proteins of MERS, SARS and SARS2 coronaviruses that infect humans

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246150
Author(s):  
Chu-Wen Yang ◽  
Zhi-Ling Shi
Keyword(s):  
Host Cell ◽  
Virus Replication ◽  
Viral Infections ◽  
Viral Proteins ◽  
Host Cells ◽  
Host Proteins ◽  
Cell Components ◽  
Linear Motifs ◽  
Novel Coronavirus ◽  
High Possibility

A coronavirus pandemic caused by a novel coronavirus (SARS-CoV-2) has spread rapidly worldwide since December 2019. Improved understanding and new strategies to cope with novel coronaviruses are urgently needed. Viruses (especially RNA viruses) encode a limited number and size (length of polypeptide chain) of viral proteins and must interact with the host cell components to control (hijack) the host cell machinery. To achieve this goal, the extensive mimicry of SLiMs in host proteins provides an effective strategy. However, little is known regarding SLiMs in coronavirus proteins and their potential targets in host cells. The objective of this study is to uncover SLiMs in coronavirus proteins that are present within host cells. These SLiMs have a high possibility of interacting with host intracellular proteins and hijacking the host cell machinery for virus replication and dissemination. In total, 1,479 SLiM hits were identified in the 16 proteins of 590 coronaviruses infecting humans. Overall, 106 host proteins were identified that may interact with SLiMs in 16 coronavirus proteins. These SLiM-interacting proteins are composed of many intracellular key regulators, such as receptors, transcription factors and kinases, and may have important contributions to virus replication, immune evasion and viral pathogenesis. A total of 209 pathways containing proteins that may interact with SLiMs in coronavirus proteins were identified. This study uncovers potential mechanisms by which coronaviruses hijack the host cell machinery. These results provide potential therapeutic targets for viral infections.

scholarly journals Legionella Subvert the Functions of Rab1 and Sec22b to Create a Replicative Organelle

2004 ◽  
Vol 199 (9) ◽  
pp. 1201-1211 ◽  
Author(s):  
Jonathan C. Kagan ◽  
Mary-Pat Stein ◽  
Marc Pypaert ◽  
Craig R. Roy
Keyword(s):  
Endoplasmic Reticulum ◽  
Legionella Pneumophila ◽  
Molecular Mechanisms ◽  
Bacterial Pathogen ◽  
Host Cells ◽  
Intracellular Growth ◽  
Host Proteins ◽  
Morphological Studies ◽  
Bacterial Replication ◽  
Inhibition Studies

Legionella pneumophila is a bacterial pathogen that infects eukaryotic host cells and replicates inside a specialized organelle that is morphologically similar to the endoplasmic reticulum (ER). To better understand the molecular mechanisms governing transport of the Legionella-containing vacuole (LCV), we have identified host proteins that participate in the conversion of the LCV into a replicative organelle. Our data show that Rab1 is recruited to the LCV within minutes of uptake. Rab1 recruitment to the LCV precedes remodeling of this compartment by ER-derived vesicles. Genetic inhibition studies demonstrate that Rab1 is important for the recruitment of ER-derived vesicles to the LCV and that inhibiting Rab1 function abrogates intracellular growth of Legionella. Morphological studies indicate that the Sec22b protein is located on ER-derived vesicles recruited to the LCV and that Sec22b is delivered to the LCV membrane. Sec22b function was found to be important for biogenesis of the specialized organelle that supports Legionella replication. These studies demonstrate that Legionella has the ability to subvert Rab1 and Sec22b function to facilitate the transport and fusion of ER-derived vesicles with the LCV, resulting in the formation of a specialized organelle that can support bacterial replication.

scholarly journals Enteropathogenic Escherichia coli (EPEC) Tir Receptor Molecule Does Not Undergo Full Modification When Introduced into Host Cells by EPEC-Independent Mechanisms

2001 ◽  
Vol 69 (3) ◽  
pp. 1444-1453 ◽  
Author(s):  
Brendan Kenny ◽  
Jonathan Warawa
Keyword(s):  
Escherichia Coli ◽  
Molecular Mass ◽  
Type Iii Secretion ◽  
Efficiency Factor ◽  
Host Cells ◽  
Sufficient Information ◽  
Phosphorylation Event ◽  
Associated Proteins ◽  
Phosphate Groups

ABSTRACT Enteropathogenic Escherichia coli (EPEC), like many other gram-negative pathogens, encodes a type III secretion apparatus dedicated to the release of virulence-associated proteins. One such protein, Tir, is translocated into host cells, where it is modified by the addition of phosphate groups, resulting in a number of species with distinct molecular mass. One phosphorylation event, on tyrosine residue 474 of Tir, does not contribute to shifts in molecular mass but is essential for its actin-nucleating function. The role of the nonphosphotyrosine related modifications is unknown. In this paper, we demonstrate, using three different approaches, that Tir does not encode sufficient information to facilitate its complete modification when introduced into host cells in EPEC-independent mechanisms. Each system revealed that Tir is a substrate for a host kinase whose action results in its partial modification to a form similar to one evident in EPEC-infected host cells. Further Tir modification could not be induced by infecting cells with EPEC, suggesting that Tir must be coexpressed with other EPEC factors to enable its full modification within host cells. One approach usedYersinia spp. to deliver Tir into host cells, and this system revealed that Tir secretion and translocation can occur in the absence of the Tir chaperone molecule, CesT (formerly known as OrfU). CesT was found to be an efficiency factor which was not required, unlike in EPEC, for Tir stability, indicating that it may function to guide Tir to the translocation apparatus or maintain it in a secretion-competent form.

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