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Viruses
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Host Cell-Virus Interaction
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Host Cell-Virus Interaction

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 59363

Special Issue Editors

Dr. Parikshit Bagchi

E-Mail Website
Guest Editor
Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, MO 63130, USA
Interests: host cell-virus interaction; intracellular trafficking of virus; membrane trafficking; non-enveloped viruses; positive sense RNA viruses
Special Issues, Collections and Topics in MDPI journals
Dr. Anupam Mukherjee

E-Mail Website
Guest Editor
Division of Virology, ICMR-National AIDS Research Institute, Pune, Maharashtra 411026, India
Interests: RNA virus; viral pathogenesis; host cell–virus interaction; RNAi; small RNA as therapeutics; targeted delivery; virus and cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Every virus needs to hijack a host cell, be it a plant, animal, insect, or even a bacterial cell, to replicate and survive at the cost of its host. It is the interactions of the virus with the host cell that holds the deepest and darkest secrets of the virus, the unravelling of which opens multiple avenues in anti-viral research. The study of host cell-virus interaction not only provides important information about virus pathogenesis; it also often has great importance in other fields of research, especially in the field of cell biology and immunology. There are several instances where novel cellular functions of a host protein were revealed by studying host cell-virus interaction. This valuable information can go a long way in understanding interactions with other related viruses as well. The regulation of cellular immune responses is another significant component of viral pathogenesis. Important knowledge regarding immunological modulation after viral infection can help to establish strategies to fight against viral infection. In this special issue, we will focus on studies related to the exploitation of host cells by viruses for successful infection, and will highlight the counteractive host cell measures employed in order to win the war against the viruses.

Dr. Parikshit Bagchi
Dr. Anupam Mukherjee
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • virus
  • host cell
  • host-virus interaction
  • virus entry
  • virus assembly and egress
  • viral replication and pathogenesis
  • viral immune evasion
  • anti-viral strategies
  • intracellular trafficking of virus

Published Papers (14 papers)

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Editorial

Jump to: Research, Review

3 pages, 177 KiB  
Editorial
Special Issue: Host Cell–Virus Interaction
by Anupam Mukherjee and Parikshit Bagchi
Viruses 2022, 14(3), 615; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030615 - 16 Mar 2022
Viewed by 1398
Abstract
As rightly put by Nobel Laureate Joshua Lederberg, “the single biggest threat to man’s continued dominance on the planet is the Virus” [...] Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)

Research

Jump to: Editorial, Review

22 pages, 27809 KiB  
Article
Exploring New Functional Aspects of HTLV-1 RNA-Binding Protein Rex: How Does Rex Control Viral Replication?
by Kazumi Nakano, Koichi Yokoyama, Shuichi Shin, Koki Uchida, Kazuki Tsuji, Marie Tanaka, Kaoru Uchimaru and Toshiki Watanabe
Viruses 2022, 14(2), 407; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020407 - 16 Feb 2022
Cited by 4 | Viewed by 2466
Abstract
After integration to the human genome as a provirus, human T-cell leukemia virus type 1 (HTLV-1) utilizes host T cell gene expression machinery for viral replication. The viral RNA-binding protein, Rex, is known to transport unspliced/incompletely spliced viral mRNAs encoding viral structural proteins [...] Read more.
After integration to the human genome as a provirus, human T-cell leukemia virus type 1 (HTLV-1) utilizes host T cell gene expression machinery for viral replication. The viral RNA-binding protein, Rex, is known to transport unspliced/incompletely spliced viral mRNAs encoding viral structural proteins out of the nucleus to enhance virus particle formation. However, the detailed mechanism of how Rex avoids extra splicing of unspliced/incompletely spliced viral mRNAs and stabilizes them for effective translation is still unclear. To elucidate the underlying molecular mechanism of Rex function, we comprehensively analyzed the changes in gene expression and splicing patterns in Rex-overexpressing T cells. In addition, we identified 81 human proteins interacting with Rex, involved in transcription, splicing, translation, and mRNA quality control. In particular, Rex interacts with NONO and SFPQ, which play important roles in the regulation of transcription and splicing. Accordingly, expression profiles and splicing patterns of a wide variety of genes are significantly changed in Rex-expressing T cells. Especially, the level of vPD-L1 mRNA that lacks the part of exon 4, thus encodes soluble PD-L1 was significantly increased in Rex-expressing cells. Overall, by integrated analysis of these three datasets, we showed for the first time that Rex intervenes the host gene expression machinery throughout the pathway, probably to escort viral unstable mRNAs from transcription (start) to translation (end). Upon exerting its function, Rex may alter the expression level and splicing patterns of various genes, thus influencing the phenotype of the host cell. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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22 pages, 3789 KiB  
Article
Elucidation of the Mechanism of Host NMD Suppression by HTLV-1 Rex: Dissection of Rex to Identify the NMD Inhibitory Domain
by Kazumi Nakano, Nobuaki Karasawa, Masaaki Hashizume, Yuetsu Tanaka, Takeo Ohsugi, Kaoru Uchimaru and Toshiki Watanabe
Viruses 2022, 14(2), 344; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020344 - 09 Feb 2022
Cited by 3 | Viewed by 2278
Abstract
The human retrovirus human T-cell leukemia virus type I (HTLV-1) infects human T cells by vertical transmission from mother to child through breast milk or horizontal transmission through blood transfusion or sexual contact. Approximately 5% of infected individuals develop adult T-cell leukemia/lymphoma (ATL) [...] Read more.
The human retrovirus human T-cell leukemia virus type I (HTLV-1) infects human T cells by vertical transmission from mother to child through breast milk or horizontal transmission through blood transfusion or sexual contact. Approximately 5% of infected individuals develop adult T-cell leukemia/lymphoma (ATL) with a poor prognosis, while 95% of infected individuals remain asymptomatic for the rest of their lives, during which time the infected cells maintain a stable immortalized latent state in the body. It is not known why such a long latent state is maintained. We hypothesize that the role of functional proteins of HTLV-1 during early infection influences the phenotype of infected cells in latency. In eukaryotic cells, a mRNA quality control mechanism called nonsense-mediated mRNA decay (NMD) functions not only to eliminate abnormal mRNAs with nonsense codons but also to target virus-derived RNAs. We have reported that HTLV-1 genomic RNA is a potential target of NMD, and that Rex suppresses NMD and stabilizes viral RNA against it. In this study, we aimed to elucidate the molecular mechanism of NMD suppression by Rex using various Rex mutant proteins. We found that region X (aa20–57) of Rex, the function of which has not been clarified, is required for NMD repression. We showed that Rex binds to Upf1, which is the host key regulator to detect abnormal mRNA and initiate NMD, through this region. Rex also interacts with SMG5 and SMG7, which play essential roles for the completion of the NMD pathway. Moreover, Rex selectively binds to Upf3B, which is involved in the normal NMD complex, and replaces it with a less active form, Upf3A, to reduce NMD activity. These results revealed that Rex invades the NMD cascade from its initiation to completion and suppresses host NMD activity to protect the viral genomic mRNA. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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18 pages, 2858 KiB  
Article
αVβ3 Integrin Expression Is Essential for Replication of Mosquito and Tick-Borne Flaviviruses in Murine Fibroblast Cells
by Vinicius Pinho dos Reis, Markus Keller, Katja Schmidt, Rainer Günter Ulrich and Martin Hermann Groschup
Viruses 2022, 14(1), 18; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010018 - 23 Dec 2021
Cited by 5 | Viewed by 3012
Abstract
The Flavivirus genus includes a number of important viruses that are pathogenic to humans and animals and are responsible for outbreaks across the globe. Integrins, a family of heterodimeric transmembrane molecules expressed in all nucleated cells mediate critical functions of cell physiology and [...] Read more.
The Flavivirus genus includes a number of important viruses that are pathogenic to humans and animals and are responsible for outbreaks across the globe. Integrins, a family of heterodimeric transmembrane molecules expressed in all nucleated cells mediate critical functions of cell physiology and cell cycle. Integrins were previously postulated to be involved in flavivirus entry and to modulate flavivirus replication efficiency. In the present study, mouse embryonic fibroblasts (MEF), lacking the expression of αVβ3 integrin (MEF-αVβ3−/−), were infected with four different flaviviruses, namely yellow fever virus (YFV), West Nile virus (WNV), Usutu virus (USUV) and Langat virus (LGTV). The effects of the αVβ3 integrin absence in double-knockout MEF-αVβ3−/− on flavivirus binding, internalization and replication were compared to the respective wild-type cells. Binding to the cell surface for all four flaviviruses was not affected by the ablation of αVβ3 integrin, whereas internalization of USUV and WNV was slightly affected by the loss of αVβ3 integrin expression. Most interestingly, the deletion of αVβ3 integrin strongly impaired replication of all flaviviruses with a reduction of up to 99% on virus yields and a strong reduction on flavivirus anti-genome RNA synthesis. In conclusion, our results demonstrate that αVβ3 integrin expression in flavivirus-susceptible cell lines enhances the flavivirus replication. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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10 pages, 754 KiB  
Communication
PDZ-Containing Proteins Targeted by the ACE2 Receptor
by Célia Caillet-Saguy and Nicolas Wolff
Viruses 2021, 13(11), 2281; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112281 - 15 Nov 2021
Cited by 10 | Viewed by 2258
Abstract
Angiotensin-converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. Indeed, the first step in viral entry is the binding of the viral trimeric spike (S) protein to ACE2. Abundantly present in human epithelial cells of many organs, [...] Read more.
Angiotensin-converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. Indeed, the first step in viral entry is the binding of the viral trimeric spike (S) protein to ACE2. Abundantly present in human epithelial cells of many organs, ACE2 is also expressed in the human brain. ACE2 is a type I membrane protein with an extracellular N-terminal peptidase domain and a C-terminal collectrin-like domain that ends with a single transmembrane helix and an intracellular 44-residue segment. This C-terminal segment contains a PDZ-binding motif (PBM) targeting protein-interacting domains called PSD-95/Dlg/ZO-1 (PDZ). Here, we identified the human PDZ specificity profile of the ACE2 PBM using the high-throughput holdup assay and measuring the binding intensities of the PBM of ACE2 against the full human PDZome. We discovered 14 human PDZ binders of ACE2 showing significant binding with dissociation constants’ values ranging from 3 to 81 μM. NHERF, SHANK, and SNX27 proteins found in this study are involved in protein trafficking. The PDZ/PBM interactions with ACE2 could play a role in ACE2 internalization and recycling that could be of benefit for the virus entry. Interestingly, most of the ACE2 partners we identified are expressed in neuronal cells, such as SHANK and MAST families, and modifications of the interactions between ACE2 and these neuronal proteins may be involved in the neurological symptoms of COVID-19. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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Graphical abstract

15 pages, 4796 KiB  
Communication
Inhibition of miR-155 Promotes TGF-β Mediated Suppression of HIV Release in the Cervical Epithelial Cells
by Jyotsna Gokavi, Sharwari Sadawarte, Anant Shelke, Urmila Kulkarni-Kale, Madhuri Thakar and Vandana Saxena
Viruses 2021, 13(11), 2266; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112266 - 12 Nov 2021
Cited by 4 | Viewed by 2565
Abstract
TGF-β has been shown to play a differential role in either restricting or aiding HIV infection in different cell types, however its role in the cervical cells is hitherto undefined. Among females, more than 80% of infections occur through heterosexual contact where cervicovaginal [...] Read more.
TGF-β has been shown to play a differential role in either restricting or aiding HIV infection in different cell types, however its role in the cervical cells is hitherto undefined. Among females, more than 80% of infections occur through heterosexual contact where cervicovaginal mucosa plays a critical role, however the early events during the establishment of infection at female genital mucosa are poorly understood. We earlier showed that increased TGF-β level has been associated with cervical viral shedding in the HIV infected women, however a causal relationship could not be examined. Therefore, here we first established an in vitro cell-associated model of HIV infection in the cervical epithelial cells (ME-180) and demonstrated that TGF-β plays an important role as a negative regulator of HIV release in the infected cervical epithelial cells. Inhibition of miR-155 upregulated TGF-β signaling and mRNA expression of host restriction factors such as APOBEC-3G, IFI-16 and IFITM-3, while decreased the HIV release in ME-180 cells. To conclude, this is the first study to decipher the complex interplay between TGF-β, miR-155 and HIV release in the cervical epithelial cells. Collectively, our data suggest the plausible role of TGF-β in promoting HIV latency in cervical epithelial cells which needs further investigations. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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14 pages, 2653 KiB  
Article
IRE1-Mediated Unfolded Protein Response Promotes the Replication of Tick-Borne Flaviviruses in a Virus and Cell-Type Dependent Manner
by Veronika J. M. Breitkopf, Gerhard Dobler, Peter Claus, Hassan Y. Naim and Imke Steffen
Viruses 2021, 13(11), 2164; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112164 - 27 Oct 2021
Cited by 7 | Viewed by 2189
Abstract
Tick-borne flaviviruses (TBFV) can cause severe neurological complications in humans, but differences in tissue tropism and pathogenicity have been described for individual virus strains. Viral protein synthesis leads to the induction of the unfolded protein response (UPR) within infected cells. The IRE1 pathway [...] Read more.
Tick-borne flaviviruses (TBFV) can cause severe neurological complications in humans, but differences in tissue tropism and pathogenicity have been described for individual virus strains. Viral protein synthesis leads to the induction of the unfolded protein response (UPR) within infected cells. The IRE1 pathway has been hypothesized to support flavivirus replication by increasing protein and lipid biogenesis. Here, we investigated the role of the UPR in TBFV infection in human astrocytes, neuronal and intestinal cell lines that had been infected with tick-borne encephalitis virus (TBEV) strains Neudoerfl and MucAr-HB-171/11 as well as Langat virus (LGTV). Both TBEV strains replicated better than LGTV in central nervous system (CNS) cells. TBEV strain MucAr-HB-171/11, which is associated with gastrointestinal symptoms, replicated best in intestinal cells. All three viruses activated the inositol-requiring enzyme 1 (IRE1) pathway via the X-box binding protein 1 (XBP1). Interestingly, the neurotropic TBEV strain Neudoerfl induced a strong upregulation of XBP1 in all cell types, but with faster kinetics in CNS cells. In contrast, TBEV strain MucAr-HB-171/11 failed to activate the IRE1 pathway in astrocytes. The low pathogenic LGTV led to a mild induction of IRE1 signaling in astrocytes and intestinal cells. When cells were treated with IRE1 inhibitors prior to infection, TBFV replication in astrocytes was significantly reduced. This confirms a supporting role of the IRE1 pathway for TBFV infection in relevant viral target cells and suggests a correlation between viral tissue tropism and the cell-type dependent induction of the unfolded protein response. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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15 pages, 1963 KiB  
Article
Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages
by Hannah S. Eisfeld, Alexander Simonis, Sandra Winter, Jason Chhen, Luisa J. Ströh, Thomas Krey, Manuel Koch, Sebastian J. Theobald and Jan Rybniker
Viruses 2021, 13(10), 2076; https://0-doi-org.brum.beds.ac.uk/10.3390/v13102076 - 15 Oct 2021
Cited by 21 | Viewed by 4739
Abstract
Infections with viral pathogens are widespread and can cause a variety of different diseases. In-depth knowledge about viral triggers initiating an immune response is necessary to decipher viral pathogenesis. Inflammasomes, as part of the innate immune system, can be activated by viral pathogens. [...] Read more.
Infections with viral pathogens are widespread and can cause a variety of different diseases. In-depth knowledge about viral triggers initiating an immune response is necessary to decipher viral pathogenesis. Inflammasomes, as part of the innate immune system, can be activated by viral pathogens. However, viral structural components responsible for inflammasome activation remain largely unknown. Here we analyzed glycoproteins derived from SARS-CoV-1/2, HCMV and HCV, required for viral entry and fusion, as potential triggers of NLRP3 inflammasome activation and pyroptosis in THP-1 macrophages. All tested glycoproteins were able to potently induce NLRP3 inflammasome activation, indicated by ASC-SPECK formation and secretion of cleaved IL-1β. Lytic cell death via gasdermin D (GSDMD), pore formation, and pyroptosis are required for IL-1β release. As a hallmark of pyroptosis, we were able to detect cleavage of GSDMD and, correspondingly, cell death in THP-1 macrophages. CRISPR-Cas9 knockout of NLRP3 and GSDMD in THP-1 macrophages confirmed and strongly support the evidence that viral glycoproteins can act as innate immunity triggers. With our study, we decipher key mechanisms of viral pathogenesis by showing that viral glycoproteins potently induce innate immune responses. These insights could be beneficial in vaccine development and provide new impulses for the investigation of vaccine-induced innate immunity. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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17 pages, 1107 KiB  
Article
Role of Serum Vitamin D, Interleukin 13, and microRNA-135a in Hepatocellular Carcinoma and Treatment Failure in Egyptian HCV-Infected Patients Receiving Direct Antiviral Agents
by Mohamed E. Ali, Hamada M. Halby, Mamdouh Yones Ali, Elham Ahmed Hassan, Mohamed A. El-Mokhtar, Ibrahim M. Sayed, Marwa M. Thabet, Magdy Fouad, Ahmed M. El-Ashmawy and Zainab Gaber Mahran
Viruses 2021, 13(10), 2008; https://0-doi-org.brum.beds.ac.uk/10.3390/v13102008 - 06 Oct 2021
Cited by 3 | Viewed by 1943
Abstract
Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of [...] Read more.
Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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10 pages, 1482 KiB  
Article
HTLV-2 Encoded Antisense Protein APH-2 Suppresses HIV-1 Replication
by Rajkumar Londhe and Smita Kulkarni
Viruses 2021, 13(8), 1432; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081432 - 23 Jul 2021
Cited by 5 | Viewed by 2047
Abstract
Antisense protein of Human T-cell Leukemia Virus Type 2 (HTLV-2), also called APH-2, negatively regulates the HTLV-2 and helps the virus to maintain latency via scheming the transcription. Despite the remarkable occurrence of HTLV-2/HIV-1 co-infection, the role of APH-2 influencing HIV-1 replication kinetics [...] Read more.
Antisense protein of Human T-cell Leukemia Virus Type 2 (HTLV-2), also called APH-2, negatively regulates the HTLV-2 and helps the virus to maintain latency via scheming the transcription. Despite the remarkable occurrence of HTLV-2/HIV-1 co-infection, the role of APH-2 influencing HIV-1 replication kinetics is poorly understood and needs investigation. In this study, we investigated the plausible role of APH-2 regulating HIV-1 replication. Herein, we report that the overexpression of APH-2 not only hampered the release of HIV-1 pNL4.3 from 293T cells in a dose-dependent manner but also affected the cellular gag expression. A similar and consistent effect of APH-2 overexpression was also observed in case of HIV-1 gag expression vector HXB2 pGag-EGFP. APH-2 overexpression also inhibited the ability of HIV-1 Tat to transactivate the HIV-1 LTR-driven expression of luciferase. Furthermore, the introduction of mutations in the IXXLL motif at the N-terminal domain of APH-2 reverted the inhibitory effect on HIV-1 Tat-mediated transcription, suggesting the possible role of this motif towards the downregulation of Tat-mediated transactivation. Overall, these findings indicate that the HTLV-2 APH-2 may affect the HIV-1 replication at multiple levels by (a) inhibiting the Tat-mediated transactivation and (b) hampering the virus release by affecting the cellular gag expression. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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22 pages, 2726 KiB  
Article
Viperin, an IFN-Stimulated Protein, Delays Rotavirus Release by Inhibiting Non-Structural Protein 4 (NSP4)-Induced Intrinsic Apoptosis
by Rakesh Sarkar, Satabdi Nandi, Mahadeb Lo, Animesh Gope and Mamta Chawla-Sarkar
Viruses 2021, 13(7), 1324; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071324 - 08 Jul 2021
Cited by 11 | Viewed by 3352
Abstract
Viral infections lead to expeditious activation of the host’s innate immune responses, most importantly the interferon (IFN) response, which manifests a network of interferon-stimulated genes (ISGs) that constrain escalating virus replication by fashioning an ill-disposed environment. Interestingly, most viruses, including rotavirus, have evolved [...] Read more.
Viral infections lead to expeditious activation of the host’s innate immune responses, most importantly the interferon (IFN) response, which manifests a network of interferon-stimulated genes (ISGs) that constrain escalating virus replication by fashioning an ill-disposed environment. Interestingly, most viruses, including rotavirus, have evolved numerous strategies to evade or subvert host immune responses to establish successful infection. Several studies have documented the induction of ISGs during rotavirus infection. In this study, we evaluated the induction and antiviral potential of viperin, an ISG, during rotavirus infection. We observed that rotavirus infection, in a stain independent manner, resulted in progressive upregulation of viperin at increasing time points post-infection. Knockdown of viperin had no significant consequence on the production of total infectious virus particles. Interestingly, substantial escalation in progeny virus release was observed upon viperin knockdown, suggesting the antagonistic role of viperin in rotavirus release. Subsequent studies unveiled that RV-NSP4 triggered relocalization of viperin from the ER, the normal residence of viperin, to mitochondria during infection. Furthermore, mitochondrial translocation of NSP4 was found to be impeded by viperin, leading to abridged cytosolic release of Cyt c and subsequent inhibition of intrinsic apoptosis. Additionally, co-immunoprecipitation studies revealed that viperin associated with NSP4 through regions including both its radical SAM domain and its C-terminal domain. Collectively, the present study demonstrated the role of viperin in restricting rotavirus egress from infected host cells by modulating NSP4 mediated apoptosis, highlighting a novel mechanism behind viperin’s antiviral action in addition to the intricacy of viperin–virus interaction. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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Review

Jump to: Editorial, Research

20 pages, 4242 KiB  
Review
Dynamic, but Not Necessarily Disordered, Human-Virus Interactions Mediated through SLiMs in Viral Proteins
by Heidy Elkhaligy, Christian A. Balbin, Jessica L. Gonzalez, Teresa Liberatore and Jessica Siltberg-Liberles
Viruses 2021, 13(12), 2369; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122369 - 26 Nov 2021
Cited by 10 | Viewed by 2934
Abstract
Most viruses have small genomes that encode proteins needed to perform essential enzymatic functions. Across virus families, primary enzyme functions are under functional constraint; however, secondary functions mediated by exposed protein surfaces that promote interactions with the host proteins may be less constrained. [...] Read more.
Most viruses have small genomes that encode proteins needed to perform essential enzymatic functions. Across virus families, primary enzyme functions are under functional constraint; however, secondary functions mediated by exposed protein surfaces that promote interactions with the host proteins may be less constrained. Viruses often form transient interactions with host proteins through conformationally flexible interfaces. Exposed flexible amino acid residues are known to evolve rapidly suggesting that secondary functions may generate diverse interaction potentials between viruses within the same viral family. One mechanism of interaction is viral mimicry through short linear motifs (SLiMs) that act as functional signatures in host proteins. Viral SLiMs display specific patterns of adjacent amino acids that resemble their host SLiMs and may occur by chance numerous times in viral proteins due to mutational and selective processes. Through mimicry of SLiMs in the host cell proteome, viruses can interfere with the protein interaction network of the host and utilize the host-cell machinery to their benefit. The overlap between rapidly evolving protein regions and the location of functionally critical SLiMs suggest that these motifs and their functional potential may be rapidly rewired causing variation in pathogenicity, infectivity, and virulence of related viruses. The following review provides an overview of known viral SLiMs with select examples of their role in the life cycle of a virus, and a discussion of the structural properties of experimentally validated SLiMs highlighting that a large portion of known viral SLiMs are devoid of predicted intrinsic disorder based on the viral SLiMs from the ELM database. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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20 pages, 5806 KiB  
Review
Dengue Virus Infection: A Tale of Viral Exploitations and Host Responses
by Nikita Nanaware, Anwesha Banerjee, Satarupa Mullick Bagchi, Parikshit Bagchi and Anupam Mukherjee
Viruses 2021, 13(10), 1967; https://0-doi-org.brum.beds.ac.uk/10.3390/v13101967 - 30 Sep 2021
Cited by 35 | Viewed by 20232
Abstract
Dengue is a mosquito-borne viral disease (arboviral) caused by the Dengue virus. It is one of the prominent public health problems in tropical and subtropical regions with no effective vaccines. Every year around 400 million people get infected by the Dengue virus, with [...] Read more.
Dengue is a mosquito-borne viral disease (arboviral) caused by the Dengue virus. It is one of the prominent public health problems in tropical and subtropical regions with no effective vaccines. Every year around 400 million people get infected by the Dengue virus, with a mortality rate of about 20% among the patients with severe dengue. The Dengue virus belongs to the Flaviviridae family, and it is an enveloped virus with positive-sense single-stranded RNA as the genetic material. Studies of the infection cycle of this virus revealed potential host targets important for the virus replication cycle. Here in this review article, we will be discussing different stages of the Dengue virus infection cycle inside mammalian host cells and how host proteins are exploited by the virus in the course of infection as well as how the host counteracts the virus by eliciting different antiviral responses. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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26 pages, 2870 KiB  
Review
Advancing Our Understanding of Corneal Herpes Simplex Virus-1 Immune Evasion Mechanisms and Future Therapeutics
by Emily Greenan, Sophie Gallagher, Rana Khalil, Conor C. Murphy and Joan Ní Gabhann-Dromgoole
Viruses 2021, 13(9), 1856; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091856 - 17 Sep 2021
Cited by 10 | Viewed by 5405
Abstract
Herpes stromal keratitis (HSK) is a disease that commonly affects the cornea and external eye and is caused by Herpes Simplex Virus type 1 (HSV-1). This virus infects approximately 66% of people worldwide; however, only a small portion of these people will develop [...] Read more.
Herpes stromal keratitis (HSK) is a disease that commonly affects the cornea and external eye and is caused by Herpes Simplex Virus type 1 (HSV-1). This virus infects approximately 66% of people worldwide; however, only a small portion of these people will develop symptoms in their lifetime. There is no cure or vaccine available for HSV-1; however, there are treatments available that aim to control the inflammation caused by the virus and prevent its recurrence. While these treatments are beneficial to those suffering with HSK, there is a need for more effective treatments to minimise the need for topical steroids, which can have harmful effects, and to prevent bouts of disease reactivation, which can lead to progressive corneal scarring and visual impairment. This review details the current understanding of HSV-1 infection and discusses potential novel treatment options including microRNAs, TLRs, mAbs, and aptamers. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction)
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