scholarly journals Cross Talk on SARS-CoV-2 and Human Immunity

2021 ◽  
Vol 16 (2) ◽  
pp. 51-59
Author(s):  
I. F Chukwuma ◽  
V.O. Apeh ◽  
J. Emaimo
Keyword(s):  
Antigen Presentation ◽  
Case Fatality ◽  
Membrane Vesicles ◽  
Adaptor Proteins ◽  
Cd8 Cells ◽  
Viral Interactions ◽  
Management And Development ◽  
Human Immune Response ◽  
Infected Cells ◽  
Human Immunity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is now the leading cause of death globally. This review elaborated the human immune response to SARSCoV-2 and its immune evasion mechanisms as well as factors that determine the case fatality rate and effective immunity using articles selected from PubMed, Medline, Google Scholar and Science Direct that provided an in-depth knowledge of the immunopathogenesis of SARS-CoV-2. Findings from the forty eligible reviewed articles revealed that the host-viral interaction to SARS-CoV-2 involves the recognition of SARS-CoV-2, recruitment of adaptor proteins and antigen presentation which activates both innate and adaptive immunity involved in inhibition of viral replication (interferons), destruction of virus-infected cells (natural killer cells and CD8 cells) and viral clearance. However, SARS-CoV-2 subverts human immunity using multiple strategies such as production of double membrane vesicles, repression of adaptor proteins, interferons and antigen presentation. Accumulating shreds of evidence have shown that several factors such as age, sex, comorbidities, obesity, and lifestyle factors affect immune responsiveness to SARS-CoV-2. Hence, better knowledge of the viral interactions with the host and factors determining prevalence and severity is fundamental to the management and development of effective and biocompatible prophylactic and therapeutic options. 

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Retention of adenovirus E19 glycoprotein in the endoplasmic reticulum is essential to its ability to block antigen presentation.

1991 ◽  
Vol 174 (6) ◽  
pp. 1629-1637 ◽  
Author(s):  
J H Cox ◽  
J R Bennink ◽  
J W Yewdell
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Antigen Presentation ◽  
Viral Proteins ◽  
Genetically Engineered ◽  
Class I ◽  
Wild Type ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Lumenal Domain

The E3/19K glycoprotein of adenovirus functions to diminish recognition of adenovirus-infected cells by major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTLs) by binding intracellular class I molecules and preventing them from reaching the plasma membrane. In the present study we have characterized the nature of the interaction between E3/19K and the H-2Kd (Kd) molecule. An E3/19K molecule genetically engineered to terminate six residues from its normal COOH terminus (delta E19), was found to associate with Kd in a manner indistinguishable from wild-type E3/19K. Unlike E3/19K, however, delta E19 was transported through the Golgi complex to the plasma membrane, where it could be detected biochemically and immunocytochemically using a monoclonal antibody specific for the lumenal domain of E3/19K. Importantly, delta E19 also differed from E3/19K in being unable to prevent the presentation of Kd-restricted viral proteins to CTLs. This is unlikely to be due to delta E19 having a lower avidity for Kd than E3/19K, since delta E19 was able to compete with E3/19K for Kd binding, both physically, and functionally in nullifying the E3/19K blockade of antigen presentation. These findings indicate that the ability of E3/19K to block antigen presentation is due solely to its ability to retain newly synthesized class I molecules in the endoplasmic reticulum.

scholarly journals Ultrastructural analysis of SARS-CoV-2 interactions with the host cell via high resolution scanning electron microscopy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lucio Ayres Caldas ◽  
Fabiana Avila Carneiro ◽  
Luiza Mendonça Higa ◽  
Fábio Luiz Monteiro ◽  
Gustavo Peixoto da Silva ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
High Resolution ◽  
Vero Cells ◽  
Viral Interactions ◽  
Viral Particles ◽  
Direct Cell ◽  
Infected Cells ◽  
Scanning Electron ◽  
Intercellular Connections

Abstract SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Here, we investigated the interaction of this new coronavirus with Vero cells using high resolution scanning electron microscopy. Surface morphology, the interior of infected cells and the distribution of viral particles in both environments were observed 2 and 48 h after infection. We showed areas of viral processing, details of vacuole contents, and viral interactions with the cell surface. Intercellular connections were also approached, and viral particles were adhered to these extensions suggesting direct cell-to-cell transmission of SARS-CoV-2.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus Nonstructural Proteins 3, 4, and 6 Induce Double-Membrane Vesicles

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Megan M. Angelini ◽  
Marzieh Akhlaghpour ◽  
Benjamin W. Neuman ◽  
Michael J. Buchmeier
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Host Cell ◽  
Rna Viruses ◽  
Membrane Vesicles ◽  
Full Length ◽  
Nonstructural Proteins ◽  
Human Coronavirus ◽  
Double Membrane ◽  
Infected Cells ◽  
Proliferation Ability

ABSTRACTCoronaviruses (CoV), like other positive-stranded RNA viruses, redirect and rearrange host cell membranes for use as part of the viral genome replication and transcription machinery. Specifically, coronaviruses induce the formation of double-membrane vesicles in infected cells. Although these double-membrane vesicles have been well characterized, the mechanism behind their formation remains unclear, including which viral proteins are responsible. Here, we use transfection of plasmid constructs encoding full-length versions of the three transmembrane-containing nonstructural proteins (nsps) of the severe acute respiratory syndrome (SARS) coronavirus to examine the ability of each to induce double-membrane vesicles in tissue culture. nsp3 has membrane disordering and proliferation ability, both in its full-length form and in a C-terminal-truncated form. nsp3 and nsp4 working together have the ability to pair membranes. nsp6 has membrane proliferation ability as well, inducing perinuclear vesicles localized around the microtubule organizing center. Together, nsp3, nsp4, and nsp6 have the ability to induce double-membrane vesicles that are similar to those observed in SARS coronavirus-infected cells. This activity appears to require the full-length form of nsp3 for action, as double-membrane vesicles were not seen in cells coexpressing the C-terminal truncation nsp3 with nsp4 and nsp6.IMPORTANCEAlthough the majority of infections caused by coronaviruses in humans are relatively mild, the SARS outbreak of 2002 to 2003 and the emergence of the human coronavirus Middle Eastern respiratory syndrome (MERS-CoV) in 2012 highlight the ability of these viruses to cause severe pathology and fatality. Insight into the molecular biology of how coronaviruses take over the host cell is critical for a full understanding of any known and possible future outbreaks caused by these viruses. Additionally, since membrane rearrangement is a tactic used by all known positive-sense single-stranded RNA viruses, this work adds to that body of knowledge and may prove beneficial in the development of future therapies not only for human coronavirus infections but for other pathogens as well.

scholarly journals Cytomegalovirus inhibition of extrinsic apoptosis determines fitness and resistance to cytotoxic CD8 T cells

2020 ◽  
Vol 117 (23) ◽  
pp. 12961-12968 ◽  
Author(s):  
M. Zeeshan Chaudhry ◽  
Rosaely Casalegno-Garduno ◽  
Katarzyna M. Sitnik ◽  
Bahram Kasmapour ◽  
Ann-Kathrin Pulm ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Cell Function ◽  
Death Receptor ◽  
Cd8 T Cell ◽  
Cytotoxic T Cell ◽  
Caspase 8 ◽  
Infected Cells

Viral immune evasion is currently understood to focus on deflecting CD8 T cell recognition of infected cells by disrupting antigen presentation pathways. We evaluated viral interference with the ultimate step in cytotoxic T cell function, the death of infected cells. The viral inhibitor of caspase-8 activation (vICA) conserved in human cytomegalovirus (HCMV) and murine CMV (MCMV) prevents the activation of caspase-8 and proapoptotic signaling. We demonstrate the key role of vICA from either virus, in deflecting antigen-specific CD8 T cell-killing of infected cells. vICA-deficient mutants, lacking either UL36 or M36, exhibit greater susceptibility to CD8 T cell control than mutants lacking the set of immunoevasins known to disrupt antigen presentation via MHC class I. This difference is evident during infection in the natural mouse host infected with MCMV, in settings where virus-specific CD8 T cells are adoptively transferred. Finally, we identify the molecular mechanism through which vICA acts, demonstrating the central contribution of caspase-8 signaling at a point of convergence of death receptor-induced apoptosis and perforin/granzyme-dependent cytotoxicity.

scholarly journals Dynamics of Coronavirus Replication-Transcription Complexes

2009 ◽  
Vol 84 (4) ◽  
pp. 2134-2149 ◽  
Author(s):  
Marne C. Hagemeijer ◽  
Monique H. Verheije ◽  
Mustafa Ulasli ◽  
Indra A. Shaltiël ◽  
Lisa A. de Vries ◽  
...  
Keyword(s):  
Live Cell Imaging ◽  
Nonstructural Protein ◽  
Membrane Vesicles ◽  
Dependent Manner ◽  
C Terminus ◽  
Efficient Replication ◽  
Infected Cells ◽  
Biochemical Analyses ◽  
Transcription Complexes ◽  
Cytoplasmic Side

ABSTRACT Coronaviruses induce in infected cells the formation of double-membrane vesicles (DMVs) in which the replication-transcription complexes (RTCs) are anchored. To study the dynamics of these coronavirus replicative structures, we generated recombinant murine hepatitis coronaviruses that express tagged versions of the nonstructural protein nsp2. We demonstrated by using immunofluorescence assays and electron microscopy that this protein is recruited to the DMV-anchored RTCs, for which its C terminus is essential. Live-cell imaging of infected cells demonstrated that small nsp2-positive structures move through the cytoplasm in a microtubule-dependent manner. In contrast, large fluorescent structures are rather immobile. Microtubule-mediated transport of DMVs, however, is not required for efficient replication. Biochemical analyses indicated that the nsp2 protein is associated with the cytoplasmic side of the DMVs. Yet, no recovery of fluorescence was observed when (part of) the nsp2-positive foci were bleached. This result was confirmed by the observation that preexisting RTCs did not exchange fluorescence after fusion of cells expressing either a green or a red fluorescent nsp2. Apparently, nsp2, once recruited to the RTCs, is not exchanged with nsp2 present in the cytoplasm or at other DMVs. Our data show a remarkable resemblance to results obtained recently by others with hepatitis C virus. The observations point to intriguing and as yet unrecognized similarities between the RTC dynamics of different plus-strand RNA viruses.

Regulation and mechanisms of extracellular vesicle biogenesis and secretion

2018 ◽  
Vol 62 (2) ◽  
pp. 125-133 ◽  
Author(s):  
Crislyn D’Souza-Schorey ◽  
Jeffrey S. Schorey
Keyword(s):  
Tumor Microenvironment ◽  
Intercellular Communication ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Systemic Delivery ◽  
Heterogeneous Membrane ◽  
Vesicle Biogenesis ◽  
Infected Cells ◽  
Pathogenic Agents

EV (extracellular vesicle) biology is a rapidly expanding field. These heterogeneous membrane vesicles, which are shed from virtually all cell types, collectively represent a new dimension of intercellular communication in normal physiology and disease. They have been shown to deliver infectious and pathogenic agents to non-infected cells whereas in cancers they are thought to condition the tumor microenvironment. Their presence in body fluids and inherent capacity for systemic delivery point to their clinical promise. All of the above only intensifies the need to better understand the classification, mode of biogenesis, and contents of the different subtypes of EVs. This article focusses on vesicle subtypes labeled as exosomes and MVs (microvesicles) and discusses the biogenesis and release of these vesicles from cells.

scholarly journals Extracellular Vesicles Mediate Receptor-Independent Transmission of Novel Tick-Borne Bunyavirus

2015 ◽  
Vol 90 (2) ◽  
pp. 873-886 ◽  
Author(s):  
Jesus A. Silvas ◽  
Vsevolod L. Popov ◽  
Adriana Paulucci-Holthauzen ◽  
Patricia V. Aguilar
Keyword(s):  
Virus Infection ◽  
Extracellular Vesicles ◽  
Virus Replication ◽  
Case Fatality ◽  
Host Protein ◽  
Host Cells ◽  
Limited Information ◽  
Recent Emergence ◽  
Infected Cells ◽  
Cytoplasmic Structures

ABSTRACTSevere fever with thrombocytopenia syndrome (SFTS) virus is a newly recognized member of the genusPhlebovirusin the familyBunyaviridae. The virus was isolated from patients presenting with hemorrhagic manifestations and an initial case fatality rate of 12 to 30% was reported. Due to the recent emergence of this pathogen, there is limited knowledge on the molecular virology of SFTS virus. Recently, we reported that the SFTS virus NSs protein inhibited the activation of the beta interferon (IFN-β) promoter. Furthermore, we also found that SFTS virus NSs relocalizes key components of the IFN response into NSs-induced cytoplasmic structures. Due to the important role these structures play during SFTS virus replication, we conducted live cell imaging studies to gain further insight into the role and trafficking of these cytoplasmic structures during virus infection. We found that some of the SFTS virus NSs-positive cytoplasmic structures were secreted to the extracellular space and endocytosed by neighboring cells. We also found that these secreted structures isolated from NSs-expressing cells and SFTS virus-infected cells were positive for the viral protein NSs and the host protein CD63, a protein associated with extracellular vesicles. Electron microscopy studies also revealed that the isolated CD63-immunoprecipitated extracellular vesicles produced during SFTS virus infection contained virions. The virions harbored within these structures were efficiently delivered to uninfected cells and were able to sustain SFTS virus replication. Altogether, these results suggest that SFTS virus exploits extracellular vesicles to mediate virus receptor-independent transmission to host cells and open the avenue for novel therapeutic strategies against SFTS virus and related pathogens.IMPORTANCESFTS virus is novel bunyavirus associated with hemorrhagic fever illness. Currently, limited information is available about SFTS virus. In the present study, we demonstrated that extracellular vesicles produced by SFTS virus-infected cells harbor infectious virions. We sought to determine whether these “infectious” extracellular vesicles can mediate transmission of the virus and confirmed that the SFTS virions were efficiently transported by these secreted structures into uninfected cells and were able to sustain efficient replication of SFTS virus. These results have significant impact on our understanding of how the novel tick-borne phleboviruses hijack cellular machineries to establish infection and point toward a novel mechanism for virus replication among arthropod-borne viruses.

scholarly journals A highly attenuated vaccinia virus strain LC16m8-based vaccine for severe fever with thrombocytopenia syndrome

2020 ◽  
Author(s):  
Tomoki Yoshikawa ◽  
Satoshi Taniguchi ◽  
Hirofumi Kato ◽  
Naoko Iwata-Yoshikawa ◽  
Hideki Tani ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Virus Strain ◽  
Protective Immunity ◽  
Case Fatality Rate ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Recombinant Vaccine ◽  
Infected Cells ◽  
Vaccinia Virus Strain ◽  
Severe Fever

AbstractSevere fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (formerly SFTS virus [SFTSV]) is an emerging hemorrhagic infectious disease with a high case-fatality rate. One of the best strategies for preventing SFTS is to develop a vaccine, which is expected to induce both humoral and cellular immunity. We applied a highly attenuated but still immunogenic vaccinia virus strain LC16m8 (m8) as a recombinant vaccine for SFTS. Recombinant m8s expressing SFTSV nucleoprotein (m8-N), envelope glycoprotein precursor (m8-GPC), and both N and GPC (m8-N+GPC) in the infected cells were generated. Both m8-GPC- and m8-N+GPC-infected cells were confirmed to produce SFTSV-like-particles (VLP) in vitro, and the N was incorporated in the VLP produced by the infection of cells with m8-N+GPC. Specific antibodies to SFTSV were induced in mice inoculated with each of the recombinant m8s, and the mice were fully protected from lethal challenge with SFTSV at both 103 TCID50 and 105 TCID50. In mice that had been immunized with vaccinia virus strain Lister in advance of m8-based SFTSV vaccine inoculation, protective immunity against the SFTSV challenge was also conferred. The pathological analysis revealed that mice immunized with m8-GPC or m8-N+GPC did not show any histopathological changes without any viral antigen-positive cells, whereas the control mice showed focal necrosis with inflammatory infiltration with SFTSV antigen-positive cells in tissues after SFTSV challenge. The passive serum transfer experiments revealed that sera collected from mice inoculated with m8-GPC or m8-N+GPC but not with m8-N conferred protective immunity against lethal SFTSV challenge in naïve mice. On the other hand, the depletion of CD8-positive cells in vivo did not abrogate the protective immunity conferred by m8-based SFTSV vaccines. Based on these results, the recombinant m8-GPC and m8-N+GPC were considered promising vaccine candidates for SFTS.Author SummarySevere fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with a high case-fatality rate (approximately 5% to >40%). Indigenous SFTS has been reported in China, Japan, South Korea, and Vietnam. Thus, the development of an effective vaccine for SFTS is urgently needed. Vaccinia virus (VAC) was previously used as a vaccine for smallpox. Unfortunately, after these strains, the so-called second generation of VAC used during the eradication campaign was associated with severe adverse events, and the third generation of VAC strains such as LC16m8 (m8) and modified vaccinia Ankara (MVA) was established. m8 is confirmed to be highly attenuated while still maintaining immunogenicity. m8 is licensed for use in healthy people in Japan. At the present time, approximately 100,000 people have undergone vaccination with m8 without experiencing any severe postvaccine complications. At present, third-generation VAC strains are attractive for a recombinant vaccine vector, especially for viral hemorrhagic infectious diseases, such as Ebola virus disease, Lassa fever, Crimean-Congo hemorrhagic fever, and SFTS. We investigated the practicality of an m8-based recombinant vaccine for SFTS as well as other promising recombinant VAC-based vaccines for viral hemorrhagic infectious diseases.

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