The consequences of viral infection on protists.

Protists encompass a vast widely distributed group of organisms, surpassing the diversity observed in metazoans. Their diverse ecological niches and life forms are intriguing characteristics that render them valuable subjects for in-depth cell biology studies. Throughout history, viruses have played a pivotal role in elucidating complex cellular processes, particularly in the context of cellular responses to viral infections. In this comprehensive review, we provide an overview of the cellular alterations that are triggered in specific hosts following different viral infections and explore intricate biological interactions observed in experimental conditions using different host-pathogen groups.

CALANGO: A phylogeny-aware comparative genomics tool for discovering quantitative genotype-phenotype associations across species.

Living species vary significantly in phenotype and genomic content. Sophisticated statistical methods linking genes with phenotypes within a species have led to breakthroughs in complex genetic diseases and genetic breeding. Despite the abundance of genomic and phenotypic data available for thousands of species, finding genotype-phenotype associations across species is challenging due to the non-independence of species data resulting from common ancestry. To address this, we present CALANGO (comparative analysis with annotation-based genomic components), a phylogeny-aware comparative genomics tool to find homologous regions and biological roles associated with quantitative phenotypes across species. In two case studies, CALANGO identified both known and previously unidentified genotype-phenotype associations. The first study revealed unknown aspects of the ecological interaction between Escherichia coli, its integrated bacteriophages, and the pathogenicity phenotype. The second identified an association between maximum height in angiosperms and the expansion of a reproductive mechanism that prevents inbreeding and increases genetic diversity, with implications for conservation biology and agriculture.

The forgotten tale of Brazilian phage therapy.

The use of bacteriophages to treat bacterial infections (known as phage therapy) is considered a possible solution to the antimicrobial resistance crisis. However, phage therapy is not a new concept. The discovery of phages in the early 20th century was closely tied to clinical practice, and phage therapy quickly spread around the world. The use of phage therapy in South America in the previous century is still shrouded in mystery and has been mentioned only briefly in recent scientific literature. Research on Brazilian reference collections of medical texts showed that Brazil was an important, but so far little-known, player of phage therapy, uncovering interesting priority claims and missing pieces of phage therapy history. Of note, there is the widespread use of phages against bacillary dysentery and staphylococcal infections, with José da Costa Cruz from the Oswaldo Cruz Institute (Rio de Janeiro, Brazil) as Brazil's leading expert and pioneer. This Historical Review about historical phage use in Brazil fills the gaps in our knowledge about the so-called golden years of phage therapy, providing information about successful experiences that can be useful against dangerous pathogens in our time.

Expert Opinion on Three Phage Therapy Related Topics: Bacterial Phage Resistance, Phage Training and Prophages in Bacterial Production Strains.

Phage therapy is increasingly put forward as a "new" potential tool in the fight against antibiotic resistant infections. During the "Centennial Celebration of Bacteriophage Research" conference in Tbilisi, Georgia on 26-29 June 2017, an international group of phage researchers committed to elaborate an expert opinion on three contentious phage therapy related issues that are hampering clinical progress in the field of phage therapy. This paper explores and discusses bacterial phage resistance, phage training and the presence of prophages in bacterial production strains while reviewing relevant research findings and experiences. Our purpose is to inform phage therapy stakeholders such as policy makers, officials of the competent authorities for medicines, phage researchers and phage producers, and members of the pharmaceutical industry. This brief also points out potential avenues for future phage therapy research and development as it specifically addresses those overarching questions that currently call for attention whenever phages go into purification processes for application.

Mimiviruses and the Human Interferon System: Viral Evasion of Classical Antiviral Activities, But Inhibition By a Novel Interferon-ß Regulated Immunomodulatory Pathway.

In this review we discuss the role of mimiviruses as potential human pathogens focusing on clinical and evolutionary evidence. We also propose a novel antiviral immunomodulatory pathway controlled by interferon-ß (IFN-ß) and mediated by immune-responsive gene 1 (IRG1) and itaconic acid, its product. Acanthamoeba polyphaga Mimivirus (APMV) was isolated from amoebae in a hospital while investigating a pneumonia outbreak. Mimivirus ubiquity and role as protist pathogens are well understood, and its putative status as a human pathogen has been gaining strength as more evidence is being found. The study of APMV and human cells interaction revealed that the virus is able to evade the IFN system by inhibiting the regulation of interferon-stimulated genes, suggesting that the virus and humans have had host-pathogen interactions. It also has shown that the virus is capable of growing on IFN-α2, but not on IFN-ß-treated cells, hinting at an exclusive IFN-ß antiviral pathway. Our hypothesis based on preliminary data and published articles is that IFN-ß preferentially upregulates IRG1 in human macrophagic cells, which in turn produces itaconic acid. This metabolite links metabolism to antiviral activity by inactivating the virus, in a novel immunomodulatory pathway relevant for APMV infections and probably to other infectious diseases as well.

Infection of the central nervous system with dengue virus 3 genotype I causing neurological manifestations in Brazil.

A case of dengue virus 3 (DENV-3) genotype I infection with neurological manifestations occurred in Belo Horizonte, Minas Gerais in October 2012. The serotype was detected by PCR, and the genotype was assessed by sequencing and phylogenetic analysis of the C-prM region. The virus causing neurological manifestations clustered with other sequences of DENV-3 genotype I. Because neurological manifestations of DENV are possibly misdiagnosed in Brazil, this study serves as an alert of the importance of DENV diagnoses in CNS infections.

Infection of the central nervous system with dengue virus 3 genotype I causing neurological manifestations in Brazil

Abstract: A case of dengue virus 3 (DENV-3) genotype I infection with neurological manifestations occurred in Belo Horizonte, Minas Gerais in October 2012. The serotype was detected by PCR, and the genotype was assessed by sequencing and phylogenetic analysis of the C-prM region. The virus causing neurological manifestations clustered with other sequences of DENV-3 genotype I. Because neurological manifestations of DENV are possibly misdiagnosed in Brazil, this study serves as an alert of the importance of DENV diagnoses in CNS infections.

Acanthamoeba polyphaga mimivirus prevents amoebal encystment-mediating serine proteinase expression and circumvents cell encystment.

Acanthamoeba is a genus of free-living amoebas distributed worldwide. Few studies have explored the interactions between these protozoa and their infecting giant virus, Acanthamoeba polyphaga mimivirus (APMV). Here we show that, once the amoebal encystment is triggered, trophozoites become significantly resistant to APMV. Otherwise, upon infection, APMV is able to interfere with the expression of a serine proteinase related to amoebal encystment and the encystment can no longer be triggered.

Protective immunity and safety of a genetically modified influenza virus vaccine.

Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Δ) and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired (RAG -/-) immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Δ infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens.

Basal Activation of Type I Interferons (Alpha2 and Beta) and 2'5'OAS Genes: Insights into Differential Expression Profiles of Interferon System Components in Systemic Sclerosis.

Objective. Systemic sclerosis (SSc) is a complex autoimmune disease in which interferons (IFNs) may play an essential role. We hypothesized that type I and III IFNs may be found in increased levels in patients and be responsible for SSc autoimmune status. Methods. Type I and III IFN and ISG basal expression profiles were measured by qPCR using RNA from PBMCs of patients and controls . Results. Type I IFNs are increased in SSc patients, while no induction of type III IFNs was detected. This induction cannot be related to IRF7, since no upregulation of this gene was seen on patients. Of the ISGs tested, 2'5'OAS levels were increased in patients, while 6-16 and MxA levels were not. Conclusions. While there is no indication of type III IFN induction, increased levels of type I IFNs may lead to abnormal regulation of ISGs that can be responsible for immune system alterations described for SSc.

Antiviral activity of type I interferons and interleukins 29 and 28a (type III interferons) against Apeu virus.

Interferons (IFNs) are cytokines with important immunomodulatory activity in vertebrates. Although type I IFNs and interleukins (IL) 29 and 28a (type III IFNs) bind to different cellular receptors and have distinct structures, most of their biological activities are redundant. Apeu virus (APEUV) is a member of the Bunyaviridae family isolated from the Brazilian rain forest. In this paper we evaluated the antiviral activity of type I and type III IFNs against APEUV. All tested IFNs were able to induce an antiviral state against the virus in a dose-dependent way. The activity of type III IFNs did not need the presence of type I IFNs. Mixing both types of IFNs did not improve the biological activity of each type alone. The tested IFNs were also able to protect human peripheral blood mononuclear cells from infection. IFN alpha2, IFN beta, IL-29 and IL-28a induced the expression of 2',5'-oligoadenylate synthetase (2'5'OAS) and 6-16 genes. Although MxA gene was related to antiviral activity against Bunyaviruses, there was no induction of MxA in our model. We were able to show activity of type I and type III IFNs against a RNA virus, and that this activity is not dependent on MxA gene.