scholarly journals Analyses of Leishmania-LRV Co-Phylogenetic Patterns and Evolutionary Variability of Viral Proteins

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2305
Author(s):  
Alexei Y. Kostygov ◽  
Danyil Grybchuk ◽  
Yulia Kleschenko ◽  
Daniil S. Chistyakov ◽  
Alexander N. Lukashev ◽  
...  
Keyword(s):  
Rna Virus ◽  
Clinical Manifestations ◽  
Purifying Selection ◽  
Viral Proteins ◽  
Small Scale ◽  
Self Healing ◽  
Genes Encoding ◽  
Leishmania Spp ◽  
Life Threatening ◽  
Vector Borne

Leishmania spp. are important pathogens causing a vector-borne disease with a broad range of clinical manifestations from self-healing ulcers to the life-threatening visceral forms. Presence of Leishmania RNA virus (LRV) confers survival advantage to these parasites by suppressing anti-leishmanial immunity in the vertebrate host. The two viral species, LRV1 and LRV2 infect species of the subgenera Viannia and Leishmania, respectively. In this work we investigated co-phylogenetic patterns of leishmaniae and their viruses on a small scale (LRV2 in L. major) and demonstrated their predominant coevolution, occasionally broken by intraspecific host switches. Our analysis of the two viral genes, encoding the capsid and RNA-dependent RNA polymerase (RDRP), revealed them to be under the pressure of purifying selection, which was considerably stronger for the former gene across the whole tree. The selective pressure also differs between the LRV clades and correlates with the frequency of interspecific host switches. In addition, using experimental (capsid) and predicted (RDRP) models we demonstrated that the evolutionary variability across the structure is strikingly different in these two viral proteins.

scholarly journals Can We Harness Immune Responses to Improve Drug Treatment in Leishmaniasis?

2020 ◽  
Vol 8 (7) ◽  
pp. 1069
Author(s):  
Raphael Taiwo Aruleba ◽  
Katharine C. Carter ◽  
Frank Brombacher ◽  
Ramona Hurdayal
Keyword(s):  
Immune Responses ◽  
Economic Status ◽  
Clinical Manifestations ◽  
Steady Increase ◽  
Clinical Use ◽  
Self Healing ◽  
Cutaneous Lesions ◽  
Vector Borne ◽  
Visceral Disease ◽  
Control And Eradication

Leishmaniasis is a vector-borne parasitic disease that has been neglected in priority for control and eradication of malaria, tuberculosis, and HIV/AIDS. Collectively, over one seventh of the world’s population is at risk of being infected with 0.7–1.2 million new infections reported annually. Clinical manifestations range from self-healing cutaneous lesions to fatal visceral disease. The first anti-leishmanial drugs were introduced in the 1950′s and, despite several shortcomings, remain the mainstay for treatment. Regardless of this and the steady increase in infections over the years, particularly among populations of low economic status, research on leishmaniasis remains under funded. This review looks at the drugs currently in clinical use and how they interact with the host immune response. Employing chemoimmunotherapeutic approaches may be one viable alternative to improve the efficacy of novel/existing drugs and extend their lifespan in clinical use.

scholarly journals Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders with Life-Threatening Clinical Manifestations and Challenging Management

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2140
Author(s):  
Tomas Simurda ◽  
Rosanna Asselta ◽  
Jana Zolkova ◽  
Monika Brunclikova ◽  
Miroslava Dobrotova ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Phenotype ◽  
Clinical Manifestations ◽  
Compound Heterozygous ◽  
Genes Encoding ◽  
Life Threatening ◽  
Congenital Afibrinogenemia ◽  
Thrombotic Complications ◽  
Based Medicine ◽  
Processing Stability

Congenital fibrinogen disorders are rare pathologies of the hemostasis, comprising quantitative (afibrinogenemia, hypofibrinogenemia) and qualitative (dysfibrinogenemia and hypodysfibrinogenemia) disorders. The clinical phenotype is highly heterogeneous, being associated with bleeding, thrombosis, or absence of symptoms. Afibrinogenemia and hypofibrinogenemia are the consequence of mutations in the homozygous, heterozygous, or compound heterozygous state in one of three genes encoding the fibrinogen chains, which can affect the synthesis, assembly, intracellular processing, stability, or secretion of fibrinogen. In addition to standard coagulation tests depending on the formation of fibrin, diagnostics also includes global coagulation assays, which are effective in monitoring the management of replacement therapy. Genetic testing is a key point for confirming the clinical diagnosis. The identification of the precise genetic mutations of congenital fibrinogen disorders is of value to permit early testing of other at risk persons and better understand the correlation between clinical phenotype and genotype. Management of patients with afibrinogenemia is particularly challenging since there are no data from evidence-based medicine studies. Fibrinogen concentrate is used to treat bleeding, whereas for the treatment of thrombotic complications, administered low-molecular-weight heparin is most often. This review deals with updated information about afibrinogenemia and hypofibrinogenemia, contributing to the early diagnosis and effective treatment of these disorders.

scholarly journals One Health Approach to Leishmaniases: Understanding the Disease Dynamics through Diagnostic Tools

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 809 ◽  
Author(s):  
Ahyun Hong ◽  
Ricardo Andrade Zampieri ◽  
Jeffrey Jon Shaw ◽  
Lucile Maria Floeter-Winter ◽  
Maria Fernanda Laranjeira-Silva
Keyword(s):  
One Health ◽  
Environmental Changes ◽  
Clinical Manifestations ◽  
Control Measures ◽  
Sand Fly ◽  
Diagnostic Tools ◽  
Self Healing ◽  
Animal Reservoir ◽  
Vector Borne Diseases ◽  
Vector Borne

Leishmaniases are zoonotic vector-borne diseases caused by protozoan parasites of the genus Leishmania that affect millions of people around the globe. There are various clinical manifestations, ranging from self-healing cutaneous lesions to potentially fatal visceral leishmaniasis, all of which are associated with different Leishmania species. Transmission of these parasites is complex due to the varying ecological relationships between human and/or animal reservoir hosts, parasites, and sand fly vectors. Moreover, vector-borne diseases like leishmaniases are intricately linked to environmental changes and socioeconomic risk factors, advocating the importance of the One Health approach to control these diseases. The development of an accurate, fast, and cost-effective diagnostic tool for leishmaniases is a priority, and the implementation of various control measures such as animal sentinel surveillance systems is needed to better detect, prevent, and respond to the (re-)emergence of leishmaniases.

scholarly journals Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis

2019 ◽  
Vol 7 (12) ◽  
pp. 695 ◽  
Author(s):  
Camila dos Santos Meira ◽  
Lashitew Gedamu
Keyword(s):  
Immune Cells ◽  
Rna Virus ◽  
Clinical Manifestations ◽  
Host Immunity ◽  
Host Cells ◽  
Health Concern ◽  
Insect Vector ◽  
Self Healing ◽  
Cutaneous Lesions ◽  
Adaptive Immune Cells

The intracellular protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a vector-borne disease of major public health concern, estimated to affect 12 million people worldwide. The clinical manifestations of leishmaniasis are highly variable and can range from self-healing localized cutaneous lesions to life-threatening disseminated visceral disease. Once introduced into the skin by infected sandflies, Leishmania parasites interact with a variety of immune cells, such as neutrophils, monocytes, dendritic cells (DCs), and macrophages. The resolution of infection requires a finely tuned interplay between innate and adaptive immune cells, culminating with the activation of microbicidal functions and parasite clearance within host cells. However, several factors derived from the host, insect vector, and Leishmania spp., including the presence of a double-stranded RNA virus (LRV), can modulate the host immunity and influence the disease outcome. In this review, we discuss the immune mechanisms underlying the main forms of leishmaniasis, some of the factors involved with the establishment of infection and disease severity, and potential approaches for vaccine and drug development focused on host immunity.

scholarly journals Maternal toxoplasmosis and the risk of childhood autism: serological and molecular small-scale studies

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jamila S. Al Malki ◽  
Nahed Ahmed Hussien ◽  
Fuad Al Malki
Keyword(s):  
Neurodevelopmental Disorders ◽  
Repetitive Behavior ◽  
Saudi Arabian ◽  
Childhood Autism ◽  
Small Scale ◽  
Autistic Children ◽  
High Prevalence ◽  
Life Threatening ◽  
The Relationship ◽  
Delayed Language Development

Abstract Background Toxoplasmosis resulting from infection with the Toxoplasma parasite has become an endemic disease worldwide. Recently, a few studies have reported a high prevalence of Toxoplasmosis infections among Saudi Arabian women. This disease could become life threatening for pregnant women and for immunodeficient people. There is evidence that infections during pregnancy, especially in the early stages, are associated with neurodevelopmental disorders. Autism disorder represents one of the most common neurodevelopmental disorders worldwide; it is associated with delayed language development, weak communication interaction, and repetitive behavior. The relationship between prenatal toxoplasmosis and autism in childhood remains unclear. The present study aims to report a link between maternal toxoplasmosis and autistic offspring among Saudi Arabian women. Method Blood samples (36 maternal, 36 from their non-autistic children, and 36 from their autistic children) were collected for serological and molecular evaluation. Results A toxoplasmosis infection was reported for 33.34% of participants using an ELISA assay (5.56% IgG+/IgM+, 11.11% IgG−/IgM+, and 16.67% IgG+/IgM-); however, a nested PCR assay targeting B1 toxoplasmosis specific genes recorded positive tests for 80.56% of the samples. In addition, the present study detected several points of mutation of mtDNA including NADH dehydrogenase (ND1, ND4) and Cyt B genes and the nDNA pyruvate kinase (PK) gene for autistic children infected with toxoplasmosis. Conclusion Considering previous assumptions, we suggest that a maternal toxoplasmosis infection could have a role in the development of childhood autism linked to mtDNA and nDNA impairment.

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 Modulation of Autophagy by SARS-CoV-2: A Potential Threat for Cardiovascular System

2020 ◽  
Vol 11 ◽  
Author(s):  
Puneet Kaur Randhawa ◽  
Kaylyn Scanlon ◽  
Jay Rappaport ◽  
Manish K. Gupta
Keyword(s):  
Host Cell ◽  
Rna Virus ◽  
Clinical Manifestations ◽  
Cardiovascular Complications ◽  
Extracellular Proteases ◽  
Potential Threat ◽  
Surface Receptors ◽  
Drug Candidates ◽  
A Genome ◽  
Number Of Patients

Recently, we have witnessed an unprecedented increase in the number of patients suffering from respiratory tract illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 virus is a single-stranded positive-sense RNA virus with a genome size of ~29.9 kb. It is believed that the viral spike (S) protein attaches to angiotensin converting enzyme 2 cell surface receptors and, eventually, the virus gains access into the host cell with the help of intracellular/extracellular proteases or by the endosomal pathway. Once, the virus enters the host cell, it can either be degraded via autophagy or evade autophagic degradation and replicate using the virus encoded RNA dependent RNA polymerase. The virus is highly contagious and can impair the respiratory system of the host causing dyspnea, cough, fever, and tightness in the chest. This disease is also characterized by an abrupt upsurge in the levels of proinflammatory/inflammatory cytokines and chemotactic factors in a process known as cytokine storm. Certain reports have suggested that COVID-19 infection can aggravate cardiovascular complications, in fact, the individuals with underlying co-morbidities are more prone to the disease. In this review, we shall discuss the pathogenesis, clinical manifestations, potential drug candidates, the interaction between virus and autophagy, and the role of coronavirus in exaggerating cardiovascular complications.

scholarly journals The Early Transcriptional Response of Human Granulocytes to Infection with Candida albicans Is Not Essential for Killing but Reflects Cellular Communications

2006 ◽  
Vol 75 (3) ◽  
pp. 1493-1501 ◽  
Author(s):  
Chantal Fradin ◽  
Abigail L. Mavor ◽  
Günther Weindl ◽  
Martin Schaller ◽  
Karin Hanke ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mononuclear Cells ◽  
De Novo ◽  
Transcriptional Response ◽  
Mononuclear Leukocytes ◽  
General Notion ◽  
Genes Encoding ◽  
Global Transcriptional Profile ◽  
Life Threatening ◽  
Systemic Infections

ABSTRACT Candida albicans is a polymorphic opportunistic fungus that can cause life-threatening systemic infections following hematogenous dissemination in patients susceptible to nosocomial infection. Neutrophils form part of the innate immune response, which is the first line of defense against microbes and is particularly important in C. albicans infections. To compare the transcriptional response of leukocytes exposed to C. albicans, we investigated the expression of key cytokine genes in polymorphonuclear and mononuclear leukocytes after incubation with C. albicans for 1 h. Isolated mononuclear cells expressed high levels of genes encoding proinflammatory signaling molecules, whereas neutrophils exhibited much lower levels, similar to those observed in whole blood. The global transcriptional profile of neutrophils was examined by using an immunology-biased human microarray to determine whether different morphological forms or the viability of C. albicans altered the transcriptome. Hyphal cells appeared to have the broadest effect, although the most strongly induced genes were regulated independently of morphology or viability. These genes were involved in proinflammatory cell-cell signaling, cell signal transduction, and cell growth. Generally, genes encoding known components of neutrophil granules showed no upregulation at this time point; however, lactoferrin, a well-known candidacidal peptide, was secreted by neutrophils. Addition to inhibitors of RNA or protein de novo synthesis did not influence the killing activity within 30 min. These results support the general notion that neutrophils do not require gene transcription to mount an immediate and direct attack against microbes. However, neutrophils exposed to C. albicans express genes involved in communication with other immune cells.

High content screening and computational prediction reveal viral genes that suppress innate immune response

2021 ◽  
Author(s):  
Tai L Ng ◽  
Erika J Olson ◽  
Tae Yeon Yoo ◽  
H. Sloane Weiss ◽  
Yukiye Koide ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Nuclear Transport ◽  
Computational Prediction ◽  
Viral Proteins ◽  
Innate Immune ◽  
Type I ◽  
Viral Genes ◽  
Genes Encoding

Suppression of the host innate immune response is a critical aspect of viral replication. Upon infection, viruses may introduce one or more proteins that inhibit key immune pathways, such as the type I interferon pathway. However, the ability to predict and evaluate viral protein bioactivity on targeted pathways remains challenging and is typically done on a single virus/gene basis. Here, we present a medium-throughput high-content cell-based assay to reveal the immunosuppressive effects of viral proteins. To test the predictive power of our approach, we developed a library of 800 genes encoding known, predicted, and uncharacterized human viral genes. We find that previously known immune suppressors from numerous viral families such as Picornaviridae and Flaviviridae recorded positive responses. These include a number of viral proteases for which we further confirmed that innate immune suppression depends on protease activity. A class of predicted inhibitors encoded by Rhabdoviridae viruses was demonstrated to block nuclear transport, and several previously uncharacterized proteins from uncultivated viruses were shown to inhibit nuclear transport of the transcription factors NF-kB and IRF3. We propose that this pathway-based assay, together with early sequencing, gene synthesis, and viral infection studies, could partly serve as the basis for rapid in vitro characterization of novel viral proteins.

scholarly journals Cell-Mediated Responses to Human Metapneumovirus Infection

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 542
Author(s):  
Marlies Ballegeer ◽  
Xavier Saelens
Keyword(s):  
Immune Response ◽  
Rna Virus ◽  
Cell Types ◽  
Host Immune Response ◽  
Human Metapneumovirus ◽  
Comprehensive Overview ◽  
Hmpv Infection ◽  
Life Threatening ◽  
Tract Infections ◽  
Almost All

Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, this negative-stranded RNA virus has probably been circulating in the human population for many decades. Interestingly, almost all adults have serologic evidence of hMPV infection. A well-established host immune response is evoked when hMPV infection occurs. However, the virus has evolved to circumvent and even exploit the host immune response. Further, infection with hMPV induces a weak memory response, and re-infections during life are common. In this review, we provide a comprehensive overview of the different cell types involved in the immune response in order to better understand the immunopathology induced by hMPV. Such knowledge may contribute to the development of vaccines and therapeutics directed against hMPV.

Sign in / Sign up

Export Citation Format

Share Document