scholarly journals The Role of Non-Structural Protein NSs in the Pathogenesis of Severe Fever with Thrombocytopenia Syndrome

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 876
Author(s):  
Jumana Khalil ◽  
Hiroki Kato ◽  
Takashi Fujita
Keyword(s):  
Immune Responses ◽  
Antiviral Therapy ◽  
Virulence Factors ◽  
Viral Pathogenesis ◽  
Structural Proteins ◽  
Structural Protein ◽  
Therapy Development ◽  
The Many ◽  
Severe Fever

Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating viral pathogenesis and disease progression through various mechanisms. NSs has been described as a potent interferon antagonist and NF-κB agonist, two divergent signaling pathways in many immune responses upon a viral encounter. In this review, we highlight the many mechanisms used by NSs on the host that promote viral replication and hyper-inflammation. Understanding these host-pathogen interactions is crucial for antiviral therapy development.

scholarly journals Immune Checkpoint Modulation in Colorectal Cancer: What’s New and What to Expect

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Julie Jacobs ◽  
Evelien Smits ◽  
Filip Lardon ◽  
Patrick Pauwels ◽  
Vanessa Deschoolmeester
Keyword(s):  
Colorectal Cancer ◽  
Immune System ◽  
Immune Responses ◽  
Metastatic Disease ◽  
Immune Checkpoint ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
The Many ◽  
Related Mortality

Colorectal cancer (CRC), as one of the most prevalent types of cancer worldwide, is still a leading cause of cancer related mortality. There is an urgent need for more efficient therapies in metastatic disease. Immunotherapy, a rapidly expanding field of oncology, is designed to boost the body’s natural defenses to fight cancer. Of the many approaches currently under study to improve antitumor immune responses, immune checkpoint inhibition has thus far been proven to be the most effective. This review will outline the treatments that take advantage of our growing understanding of the role of the immune system in cancer, with a particular emphasis on immune checkpoint molecules, involved in CRC pathogenesis.

scholarly journals The Role of Porphyromonas gingivalis Virulence Factors in Periodontitis Immunopathogenesis

2020 ◽  
Vol 23 (1) ◽  
pp. 6-12
Author(s):  
Tienneke Riana Septiwidyati ◽  
Endang Winiati Bachtiar
Keyword(s):  
Immune Responses ◽  
Porphyromonas Gingivalis ◽  
Virulence Factors ◽  
Defense Mechanisms ◽  
Tooth Loss ◽  
Innate Immune ◽  
Not Given ◽  
Innate Immune Responses ◽  
Oral Bacterium

Porphyromonas gingivalis is an anaerobic Gram-negative oral bacterium involved in the pathogenesis of periodontitis. Periodontitis is an infection that is characterized by damage to the supporting tissues of the teeth so that it can cause tooth loss if not given treatment. P. gingivalis locally can invade periodontal tissue and avoid host defense mechanisms. This bacterium has virulence factors which can cause deregulation of innate immune responses and inflammation in the host. The role of P. gingivalis virulence factors such as capsules, fimbriae, lipopolysaccharides, and gingipain in the pathogenesis of periodontitis will be discussed in this paper.

scholarly journals Unraveling the Underlying Interaction Mechanism Between Dabie bandavirus and Innate Immune Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuan-min Zhou ◽  
Xue-jie Yu
Keyword(s):  
Interaction Mechanism ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Structural Protein ◽  
Antiviral Responses ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Severe Fever

The genus Bandavirus consists of seven tick-borne bunyaviruses, among which four are known to infect humans. Dabie bandavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), poses serious threats to public health worldwide. SFTSV is a tick-borne virus mainly reported in China, South Korea, and Japan with a mortality rate of up to 30%. To date, most immunology-related studies focused on the antagonistic role of SFTSV non-structural protein (NSs) in sequestering RIG-I-like-receptors (RLRs)-mediated type I interferon (IFN) induction and type I IFN mediated signaling pathway. It is still elusive whether the interaction of SFTSV and other conserved innate immune responses exists. As of now, no specific vaccines or therapeutics are approved for SFTSV prevention or treatments respectively, in part due to a lack of comprehensive understanding of the molecular interactions occurring between SFTSV and hosts. Hence, it is necessary to fully understand the host-virus interactions including antiviral responses and viral evasion mechanisms. In this review, we highlight the recent progress in understanding the pathogenesis of SFTS and speculate underlying novel mechanisms in response to SFTSV infection.

scholarly journals Minute virus of mice small non-structural protein NS2 localizes within, but is not required for the formation of, Smn-associated autonomous parvovirus-associated replication bodies

2005 ◽  
Vol 86 (4) ◽  
pp. 1009-1014 ◽  
Author(s):  
Philip J. Young ◽  
Ann Newman ◽  
Klaus T. Jensen ◽  
Lisa R. Burger ◽  
David J. Pintel ◽  
...  
Keyword(s):  
Virus Replication ◽  
Survival Motor Neuron ◽  
Structural Proteins ◽  
Temporal Delay ◽  
Structural Protein ◽  
Wild Type ◽  
Minute Virus Of Mice ◽  
Minute Virus ◽  
Nuclear Structures

The non-structural proteins NS1 and NS2 of the parvovirus minute virus of mice (MVM) are required for efficient virus replication. It has previously been shown that NS1 and NS2 interact and colocalize with the survival motor neuron (Smn) gene product in novel nuclear structures that are formed late in infection, termed Smn-associated APAR (autonomous parvovirus-associated replication) bodies (SAABs). It is not clear what molecular viral intermediate(s) contribute to SAAB formation. The current results address the role of NS2 in SAAB formation. In highly synchronized wild-type MVM infection of murine A92L cells, NS2 colocalizes with Smn and other SAAB constituents. An MVM mutant that does not produce NS2 still generates SAABS, albeit with a temporal delay. The lag in SAAB formation seen in the absence of NS2 is probably related to the temporal delay in virus replication, suggesting that, whilst NS2 is required for efficient viral infection, it is dispensable for SAAB formation.

scholarly journals RNA interference of rotavirus segment 11 mRNA reveals the essential role of NSP5 in the virus replicative cycle

2005 ◽  
Vol 86 (5) ◽  
pp. 1481-1487 ◽  
Author(s):  
Michela Campagna ◽  
Catherine Eichwald ◽  
Fulvia Vascotto ◽  
Oscar R. Burrone
Keyword(s):  
Rna Interference ◽  
Virus Replication ◽  
Essential Role ◽  
Genome Segment ◽  
Structural Proteins ◽  
Structural Protein ◽  
Specific Manner ◽  
Different Strains ◽  
Replicative Cycle

Rotavirus genomes contain 11 double-stranded (ds) RNA segments. Genome segment 11 encodes the non-structural protein NSP5 and, in some strains, also NSP6. NSP5 is produced soon after viral infection and localizes in cytoplasmic viroplasms, where virus replication takes place. RNA interference by small interfering (si) RNAs targeted to genome segment 11 mRNA of two different strains blocked production of NSP5 in a strain-specific manner, with a strong effect on the overall replicative cycle: inhibition of viroplasm formation, decreased production of other structural and non-structural proteins, synthesis of viral genomic dsRNA and production of infectious particles. These effects were shown not to be due to inhibition of NSP6. The results obtained strengthen the importance of secondary transcription/translation in rotavirus replication and demonstrate that NSP5 is essential for the assembly of viroplasms and virus replication.

scholarly journals Dengue Virus Non-Structural Protein 5 as a Versatile, Multi-Functional Effector in Host–Pathogen Interactions

2021 ◽  
Vol 11 ◽  
Author(s):  
Priya Bhatnagar ◽  
Gopinathan Pillai Sreekanth ◽  
Kaja Murali-Krishna ◽  
Anmol Chandele ◽  
Ramakrishnan Sitaraman
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Structural Proteins ◽  
Structural Protein ◽  
Human Virus ◽  
Human Host ◽  
Adaptive Immune ◽  
Interferon Signalling ◽  
Rna Capping ◽  
Stat Pathway

Dengue is emerging as one of the most prevalent mosquito-borne viral diseases of humans. The 11kb RNA genome of the dengue virus encodes three structural proteins (envelope, pre-membrane, capsid) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5), all of which are translated as a single polyprotein that is subsequently cleaved by viral and host cellular proteases at specific sites. Non-structural protein 5 (NS5) is the largest of the non-structural proteins, functioning as both an RNA-dependent RNA polymerase (RdRp) that replicates the viral RNA and an RNA methyltransferase enzyme (MTase) that protects the viral genome by RNA capping, facilitating polyprotein translation. Within the human host, NS5 interacts with several proteins such as those in the JAK-STAT pathway, thereby interfering with anti-viral interferon signalling. This mini-review presents annotated, consolidated lists of known and potential NS5 interactors in the human host as determined by experimental and computational approaches respectively. The most significant protein interactors and the biological pathways they participate in are also highlighted and their implications discussed, along with the specific serotype of dengue virus as appropriate. This information can potentially stimulate and inform further research efforts towards providing an integrative understanding of the mechanisms by which NS5 manipulates the human-virus interface in general and the innate and adaptive immune responses in particular.

scholarly journals Viperin, an IFN-Stimulated Protein, Delays Rotavirus Release by Inhibiting Non-Structural Protein 4 (NSP4)-Induced Intrinsic Apoptosis

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1324
Author(s):  
Rakesh Sarkar ◽  
Satabdi Nandi ◽  
Mahadeb Lo ◽  
Animesh Gope ◽  
Mamta Chawla-Sarkar
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Host Cells ◽  
Progeny Virus ◽  
Structural Protein ◽  
Intrinsic Apoptosis ◽  
Independent Manner ◽  
Rotavirus Infection ◽  
Successful Infection

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.

On Future Directions in Pathology

1982 ◽  
Vol 40 ◽  
pp. 274-277
Author(s):  
Benjamin F. Trump ◽  
Irene K. Berezesky ◽  
Raymond T. Jones
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Clinical Pathology ◽  
Future Directions ◽  
Diagnostic Pathology ◽  
The Past ◽  
Transmission Electron ◽  
Organ Systems ◽  
The Many

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.

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