The Role of Extracellular Vesicles in Viral Infection and Transmission

Extracellular vesicles (EVs) have been found to be released by any type of cell and can be retrieved in every circulating body fluid, namely blood (plasma, serum), saliva, milk, and urine. EVs were initially considered a cellular garbage disposal tool, but later it became evident that they are involved in intercellular signaling. There is evidence that viruses can use EV endocytic routes to enter uninfected cells and hijack the EV secretory pathway to exit infected cells, thus illustrating that EVs and viruses share common cell entry and biogenesis mechanisms. Moreover, EVs play a role in immune response against viral pathogens. EVs incorporate and spread both viral and host factors, thereby prompting or inhibiting immune responses towards them via a multiplicity of mechanisms. The involvement of EVs in immune responses, and their potential use as agents modulating viral infection, will be examined. Although further studies are needed, the engineering of EVs could package viral elements or host factors selected for their immunostimulatory properties, to be used as vaccines or tolerogenic tools in autoimmune diseases.

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Interplay between Cellular Metabolism and Cytokine Responses during Viral Infection

Viruses ◽

10.3390/v10100521 ◽

2018 ◽

Vol 10 (10) ◽

pp. 521 ◽

Cited By ~ 9

Author(s):

Shu Zhang ◽

Jessica Carriere ◽

Xiaoxi Lin ◽

Na Xie ◽

Pinghui Feng

Keyword(s):

Immune Responses ◽

Viral Infection ◽

Metabolic Reprogramming ◽

Biological Processes ◽

Viral Pathogens ◽

Obligate Intracellular ◽

Host Interaction ◽

Cytokine Responses ◽

Infected Cells ◽

Future Potential

Metabolism and immune responses are two fundamental biological processes that serve to protect hosts from viral infection. As obligate intracellular pathogens, viruses have evolved diverse strategies to activate metabolism, while inactivating immune responses to achieve maximal reproduction or persistence within their hosts. The two-way virus-host interaction with metabolism and immune responses choreograph cytokine production via reprogramming metabolism of infected cells/hosts. In return, cytokines can affect the metabolism of virus-infected and bystander cells to impede viral replication processes. This review aims to summarize our current understanding of the cross-talk between metabolic reprogramming and cytokine responses, and to highlight future potential research topics. Although the focus is placed on viral pathogens, relevant findings from other microbes are integrated to provide an overall picture, particularly when corresponding information on viral infection is lacking.

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Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽

10.3390/cells10071720 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1720

Author(s):

Kuo-Chieh Liao ◽

Mariano A. Garcia-Blanco

Keyword(s):

Innate Immunity ◽

Alternative Splicing ◽

Immune Responses ◽

Viral Infection ◽

Rna Splicing ◽

Type I ◽

Host Immune Responses ◽

Transcriptional Regulatory Mechanisms ◽

Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

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COVID-19 and nutritional deficiency: a review of existing knowledge

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2020-0074 ◽

2021 ◽

Vol 42 (1) ◽

pp. 77-85

Author(s):

Meghana Muthuvattur Pallath ◽

Ashok Kumar Ahirwar ◽

Satyendra Chandra Tripathi ◽

Priyanka Asia ◽

Apurva Sakarde ◽

...

Keyword(s):

Immune Responses ◽

Viral Infection ◽

Close Contact ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Antibody Affinity ◽

Global Pandemic ◽

Underlying Diseases ◽

Pro Inflammatory Cytokines

Abstract COVID-19 has resulted in an ongoing global pandemic, which spread largely among people who have had close contact with the infected person. The immunopathology of the SARS-CoV-2 virus includes the production of an excess amount of pro-inflammatory cytokines “a cytokine-storm”. The respiratory system (main), cardiovascular system and the gastrointestinal tract are the most affected body systems during viral infection. It has been found that most of the patients who require admission to hospital are elderly or have chronic underlying diseases. Higher cases of malnutrition and co-morbidities like diabetes mellitus and cardiovascular diseases are reported in elderly patients due to which, the immune system weakens and hence, the response to the virus is diminished in magnitude. A deficiency of micronutrients results in impaired immune responses leading to improper secretion of cytokines, alterations in secretory antibody response and antibody affinity which increases susceptibility to viral infection. The deficiency of various micronutrients in COVID-19 patient can be treated by appropriate nutritional supplements, prescribed after evaluating the patients’ nutritional status. Here we aim to highlight the role of a few particular nutrients namely Vitamin D, Vitamin C, Omega-3 fatty acids, Zinc and Magnesium along with the synergistic roles they play in enhancing immunity and thus, maintaining homeostasis.

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Vpr Enhances Tumor Necrosis Factor Production by HIV-1-Infected T Cells

Journal of Virology ◽

10.1128/jvi.02098-15 ◽

2015 ◽

Vol 89 (23) ◽

pp. 12118-12130 ◽

Cited By ~ 16

Author(s):

Ferdinand Roesch ◽

Léa Richard ◽

Réjane Rua ◽

Françoise Porrot ◽

Nicoletta Casartelli ◽

...

Keyword(s):

Immune Responses ◽

Proinflammatory Cytokine ◽

Tumor Necrosis ◽

Cellular Proteins ◽

Accessory Protein ◽

Infected Cells ◽

Hiv 1 ◽

Necrosis Factor ◽

Stimulation Of

ABSTRACTThe HIV-1 accessory protein Vpr displays different activities potentially impacting viral replication, including the arrest of the cell cycle in the G2phase and the stimulation of apoptosis and DNA damage response pathways. Vpr also modulates cytokine production by infected cells, but this property remains partly characterized. Here, we investigated the effect of Vpr on the production of the proinflammatory cytokine tumor necrosis factor (TNF). We report that Vpr significantly increases TNF secretion by infected lymphocytes.De novoproduction of Vpr is required for this effect. Vpr mutants known to be defective for G2cell cycle arrest induce lower levels of TNF secretion, suggesting a link between these two functions. Silencing experiments and the use of chemical inhibitors further implicated the cellular proteins DDB1 and TAK1 in this activity of Vpr. TNF secreted by HIV-1-infected cells triggers NF-κB activity in bystander cells and allows viral reactivation in a model of latently infected cells. Thus, the stimulation of the proinflammatory pathway by Vpr may impact HIV-1 replicationin vivo.IMPORTANCEThe role of the HIV-1 accessory protein Vpr remains only partially characterized. This protein is important for viral pathogenesis in infected individuals but is dispensable for viral replication in most cell culture systems. Some of the functions described for Vpr remain controversial. In particular, it remains unclear whether Vpr promotes or instead prevents proinflammatory and antiviral immune responses. In this report, we show that Vpr promotes the release of TNF, a proinflammatory cytokine associated with rapid disease progression. Using Vpr mutants or inhibiting selected cellular genes, we show that the cellular proteins DDB1 and TAK1 are involved in the release of TNF by HIV-infected cells. This report provides novel insights into how Vpr manipulates TNF production and helps clarify the role of Vpr in innate immune responses and inflammation.

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Zika virus hijacks extracellular vesicle tetraspanin pathways for cell-to-cell transmission

10.1101/2021.03.02.433679 ◽

2021 ◽

Author(s):

Sara B. York ◽

Li Sun ◽

Allaura S. Cone ◽

Leanne C. Duke ◽

Mujeeb R. Cheerathodi ◽

...

Keyword(s):

Extracellular Vesicles ◽

Intercellular Communication ◽

Zika Virus ◽

Biological Fluids ◽

Virus Transmission ◽

First Trimester ◽

Enhanced Production ◽

Infected Cells ◽

Encapsulated Structures

ABSTRACTExtracellular vesicles (EVs) are membrane-encapsulated structures released by cells which carry signaling factors, proteins and microRNAs that mediate intercellular communication. Accumulating evidence supports an important role of EVs in the progression of neurological conditions and both the spread and pathogenesis of infectious diseases. It has recently been demonstrated that EVs from Hepatitis C virus (HCV) infected individuals and cells contained replicative-competent viral RNA that was capable of infecting hepatocytes. Being a member of the same viral family, it is likely the Zika virus also hijacks EV pathways to package viral components and secrete vesicles that are infectious and potentially less immunogenic. As EVs have been shown to cross blood-brain and placental barriers, it is possible that Zika virus could usurp normal EV biology to gain access to the brain or developing fetus. Here, we demonstrate that Zika virus infected cells secrete distinct EV sub-populations with specific viral protein profiles and infectious genomes. Zika virus infection resulted in the enhanced production of EVs with varying sizes and density compared to those released from non-infected cells. We also show that the EV enriched tetraspanin CD63 regulates the release of EVs, and Zika viral genomes and capsids following infection. Overall, these findings provide evidence for an alternative means of Zika virus transmission and demonstrate the role of EV biogenesis and trafficking proteins in the modulation of Zika infection.ImportanceZika virus is a re-emerging infectious disease that spread rapidly across the Caribbean and South America. Infection of pregnant women during the first trimester has been linked to microcephaly, a neurological condition where babies are born with smaller heads due to abnormal brain development. Babies born with microcephaly can develop convulsions and suffer disabilities as they age. Despite the significance of Zika virus, little is known about how the virus infects the fetus or causes disease. Extracellular vesicles (EVs) are membrane-encapsulated structures released by cells that are present in all biological fluids. EVs carry signaling factors, proteins and microRNAs that mediate intercellular communication. EVs have been shown to be a means by which some viruses can alter cellular environments and cross previously unpassable cellular barriers. Thus gaining a greater understanding of how Zika affects EV cargo may aid in the development of better diagnostics, targeted therapeutics and prophylactic treatments.

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Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cells ◽

10.3390/cells8090968 ◽

2019 ◽

Vol 8 (9) ◽

pp. 968 ◽

Cited By ~ 6

Author(s):

Sunitha Kodidela ◽

Kelli Gerth ◽

Sanjana Haque ◽

Yuqing Gong ◽

Saifudeen Ismael ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Extracellular Vesicles ◽

Treatment Strategies ◽

Progressive Dementia ◽

Hiv Patients ◽

Age Related ◽

Infected Cells ◽

New Treatment

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

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Immune Responses against Salmonella enterica Serovar Enteritidis Infection in Virally Immunosuppressed Chickens

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.10.4.670-679.2003 ◽

2003 ◽

Vol 10 (4) ◽

pp. 670-679 ◽

Cited By ~ 37

Author(s):

Ruby R. Sheela ◽

Uma Babu ◽

Jie Mu ◽

Subbiah Elankumaran ◽

Daniel A. Bautista ◽

...

Keyword(s):

Immune Responses ◽

Salmonella Enterica ◽

Immunoglobulin A ◽

Chicken Anemia Virus ◽

Salmonella Enterica Serovar Enteritidis ◽

Limited Effect ◽

Field Situation ◽

Infected Cells ◽

Anemia Virus

ABSTRACT To understand the role of immune mechanisms in protecting chickens from Salmonella infections, we examined the immune responses of Salmonella enterica serovar Enteritidis-infected chickens and the effect of chicken anemia virus (CAV), a T-cell-targeted virus, on S. enterica serovar Enteritidis-induced immune responses. One-day-old chicks were orally inoculated with S. enterica serovar Enteritidis with or without intramuscular injection of CAV. The bacterial infection, pathology, and immune responses of chickens were evaluated at 14, 28, and 56 days postinoculation. The infection increased the levels of S. enterica serovar Enteritidis-specific mucosal immunoglobulin A (IgA), the number of gut-associated T cells, and the titer of serum IgG specific for S. enterica serovar Enteritidis surface antigens. CAV infection depressed these immune responses, especially the mucosal immune responses, but did not increase the number of S. enterica serovar Enteritidis-infected cells in the intestine. The severity of pathological lesions appeared to be reciprocal to the level of immune responses, but the S. enterica serovar Enteritidis infection persisted. These results suggest that oral infection of S. enterica serovar Enteritidis in chickens induces both mucosal and systemic immune responses, which have a limited effect on the S. enterica serovar Enteritidis infection under conditions designed to mimic the field situation.

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The role of interferon induced with helicase C domain 1 (IFIH1) in the development of type 1 diabetes mellitus

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302013000900001 ◽

2013 ◽

Vol 57 (9) ◽

pp. 667-676 ◽

Cited By ~ 5

Author(s):

Ana Paula Bouças ◽

Fernanda dos Santos de Oliveira ◽

Luis Henrique Canani ◽

Daisy Crispim

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Metabolic Decompensation ◽

Viral Pathogens ◽

Autoimmune Destruction ◽

Infected Cells ◽

Rna And Dna

Type 1 diabetes mellitus (T1DM) is a chronic, progressive, autoimmune disease characterized by metabolic decompensation frequently leading to dehydration and ketoacidosis. Viral pathogens seem to play a major role in triggering the autoimmune destruction that leads to the development of T1DM. Among several viral strains investigated so far, enteroviruses have been consistently associated with T1DM in humans. One of the mediators of viral damage is the double-stranded RNA (dsRNA) generated during replication and transcription of viral RNA and DNA. The IFIH1 gene encodes a cytoplasmic receptor of the pattern-recognition receptors (PRRs) family that recognizes dsRNA, playing a role in the innate immune response triggered by viral infection. Binding of dsRNA to this PRR triggers the release of proinflammatory cytokines, such as interferons (IFNs), which exhibit potent antiviral activity, protecting uninfected cells and inducing apoptosis of infected cells. The IFIH1 gene appears to play a major role in the development of some autoimmune diseases, and it is, therefore, a candidate gene for T1DM. Within this context, the objective of the present review was to address the role of IFIH1 in the development of T1DM.

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HIV-1 Virus Interactions With Host Proteins: Interaction of the N-terminal Domain of the HIV-1 Capsid Protein With Human Calmodulin

Natural Product Communications ◽

10.1177/1934578x19849190 ◽

2019 ◽

Vol 14 (5) ◽

pp. 1934578X1984919

Author(s):

Ywh-Min Tzou ◽

Ronald Shin ◽

N. Rama Krishna

Keyword(s):

Capsid Protein ◽

Host Factors ◽

Host Proteins ◽

Terminal Domain ◽

Immunodeficiency Virus ◽

Infected Cells ◽

Virus Interactions ◽

Precise Role ◽

Hiv 1

The human immunodeficiency virus (HIV-1 virus) exploits several host factors for assembly, infection, and replication within the infected cells. In this work, we describe the evidence for an interaction of the N-terminal domain of the HIV-1 capsid protein with human calmodulin. The precise role of this interaction within the life cycle of the HIV-1 virus is yet to be defined. Potential roles for this interaction in the viral capsid uncoating are discussed.

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Role of non-motile microtubule-associated proteins in virus trafficking

BioMolecular Concepts ◽

10.1515/bmc-2016-0018 ◽

2016 ◽

Vol 7 (5-6) ◽

pp. 283-292 ◽

Cited By ~ 3

Author(s):

Débora M. Portilho ◽

Roger Persson ◽

Nathalie Arhel

Keyword(s):

Motor Proteins ◽

Current Knowledge ◽

Cell Entry ◽

Cellular Transport ◽

Microtubule Associated Proteins ◽

Virus Trafficking ◽

Cytoskeletal Dynamics ◽

Associated Proteins ◽

Infected Cells

AbstractViruses are entirely dependent on their ability to infect a host cell in order to replicate. To reach their site of replication as rapidly and efficiently as possible following cell entry, many have evolved elaborate mechanisms to hijack the cellular transport machinery to propel themselves across the cytoplasm. Long-range movements have been shown to involve motor proteins along microtubules (MTs) and direct interactions between viral proteins and dynein and/or kinesin motors have been well described. Although less well-characterized, it is also becoming increasingly clear that non-motile microtubule-associated proteins (MAPs), including structural MAPs of the MAP1 and MAP2 families, and microtubule plus-end tracking proteins (+TIPs), can also promote viral trafficking in infected cells, by mediating interaction of viruses with filaments and/or motor proteins, and modulating filament stability. Here we review our current knowledge on non-motile MAPs, their role in the regulation of cytoskeletal dynamics and in viral trafficking during the early steps of infection.

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