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Viruses May 2022Junín virus (JUNV) belongs to the family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in... (Review)
Review
Junín virus (JUNV) belongs to the family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in Argentina. At this moment, there are no effective antiviral therapeutics to battle pathogenic arenaviruses. Cumulative reports from recent years have widely provided information on cellular factors playing key roles during JUNV infection. In this review, we summarize research on host molecular determinants that intervene in the different stages of the viral life cycle: viral entry, replication, assembly and budding. Alongside, we describe JUNV tight interplay with the innate immune system. We also review the development of different reverse genetics systems and their use as tools to study JUNV biology and its close teamwork with the host. Elucidating relevant interactions of the virus with the host cell machinery is highly necessary to better understand the mechanistic basis beyond virus multiplication, disease pathogenesis and viral subversion of the immune response. Altogether, this knowledge becomes essential for identifying potential targets for the rational design of novel antiviral treatments to combat JUNV as well as other pathogenic arenaviruses.
Topics: Antiviral Agents; Arenaviridae; Arenavirus; Hemorrhagic Fever, American; Humans; Junin virus; Virus Replication
PubMed: 35746604
DOI: 10.3390/v14061134 -
Viruses Apr 2021Rodent-borne arenaviruses have been traditionally predominantly associated with certain muroid species from genera (African arenaviruses) or with species that belong to...
Rodent-borne arenaviruses have been traditionally predominantly associated with certain muroid species from genera (African arenaviruses) or with species that belong to murid subfamily (New World arenaviruses) [...].
Topics: Amino Acid Sequence; Animals; Arenaviridae Infections; Arenavirus; Fishes; Humans; Rodentia; Snakes
PubMed: 33919632
DOI: 10.3390/v13040703 -
Viruses Mar 2024The order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses... (Review)
Review
The order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses are responsible for an increasing number of outbreaks worldwide and represent a threat to public health. Infection in humans can be asymptomatic, or it may present with a range of conditions from a mild, febrile illness to severe hemorrhagic syndromes and/or neurological complications. There is a need to develop safe and effective vaccines, a process requiring better understanding of the adaptive immune responses involved during infection. This review highlights the most recent findings regarding T cell and antibody responses to the five families with known human pathogens (, , , , and ). Future studies that define and characterize mechanistic correlates of protection against infections or disease will help inform the development of effective vaccines.
Topics: Humans; RNA Viruses; Arenaviridae; Adaptive Immunity; Vaccines
PubMed: 38543848
DOI: 10.3390/v16030483 -
Viruses Jul 2020is a family of viruses harbouring important emerging pathogens belonging to the order. Like in other segmented negative strand RNA viruses, the nucleoprotein (NP) is a... (Review)
Review
is a family of viruses harbouring important emerging pathogens belonging to the order. Like in other segmented negative strand RNA viruses, the nucleoprotein (NP) is a major actor of the viral life cycle being both (i) the necessary co-factor of the polymerase present in the L protein, and (ii) the last line of defence of the viral genome (vRNA) by physically hiding its presence in the cytoplasm. The NP is also one of the major players interfering with the immune system. Several structural studies of NP have shown that it features two domains: a globular RNA binding domain (NP-core) in its N-terminal and an exonuclease domain (ExoN) in its C-terminal. Further studies have observed that significant conformational changes are necessary for RNA encapsidation. In this review we revisited the most recent structural and functional data available on NP, compared to other nucleoproteins and explored the structural and functional implications. We review the variety of structural motif extensions involved in NP-NP binding mode. We also evaluate the major functional implications of NP interactome and the role of ExoN, thus making the NP a target of choice for future vaccine and antiviral therapy.
Topics: Arenaviridae; Nucleocapsid Proteins; Protein Structure, Tertiary; Virus Assembly
PubMed: 32708976
DOI: 10.3390/v12070772 -
Cell Reports May 2023Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for...
Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.
Topics: Humans; Lassa virus; Antibodies, Neutralizing; Lassa Fever; Glycoproteins; Antigens, Viral
PubMed: 37209096
DOI: 10.1016/j.celrep.2023.112524 -
Annual Review of Virology Sep 2017Hemorrhagic fevers caused by viruses were identified in the late 1950s in South America. These viruses have existed in their hosts, the New World rodents, for millions... (Review)
Review
Hemorrhagic fevers caused by viruses were identified in the late 1950s in South America. These viruses have existed in their hosts, the New World rodents, for millions of years. Their emergence as infectious agents in humans coincided with changes in the environment and farming practices that caused explosions in their host rodent populations. Zoonosis into humans likely occurs because the pathogenic New World arenaviruses use human transferrin receptor 1 to enter cells. The mortality rate after infection with these viruses is high, but the mechanism by which disease is induced is still not clear. Possibilities include direct effects of cellular infection or the induction of high levels of cytokines by infected sentinel cells of the immune system, leading to endothelia and thrombocyte dysfunction and neurological disease. Here we provide a review of the ecology and molecular and cellular biology of New World arenaviruses, as well as a discussion of the current animal models of infection. The development of animal models, coupled with an improved understanding of the infection pathway and host response, should lead to the discovery of new drugs for treating infections.
Topics: Animals; Antigens, CD; Arenaviridae Infections; Arenaviruses, New World; Disease Models, Animal; Hemorrhagic Fevers, Viral; Host-Pathogen Interactions; Humans; Mice; Receptors, Transferrin; Receptors, Virus; Rodentia; Zoonoses
PubMed: 28645238
DOI: 10.1146/annurev-virology-101416-042001 -
Travel Medicine and Infectious Disease 2021Bolivian hemorrhagic fever (BHF) is a sporadic high-mortality febrile illness. Two etiological agents are currently recognized: Machupo virus and Chapare virus.... (Review)
Review
Bolivian hemorrhagic fever (BHF) is a sporadic high-mortality febrile illness. Two etiological agents are currently recognized: Machupo virus and Chapare virus. Infection in humans occurs by exposure to excreta and secretions of wild native rodents in Bolivia. BHF is considered a severe disease that has three clinical phases: prodromal, hemorrhagic, and convalescent. Unspecific symptoms occur during the first phase, severe hemorrhagic manifestations occur during the second phase, and finally patients who survive experience a slow convalescent phase. The incubation period is variable and depends on host factors, viral pathogenicity, and severity of the disease. The diagnosis is primarily clinical and epidemiological, and though diagnosis should be confirmed by laboratory tests, viral agents of BHF are considered very pathogenic and need to be handled in reference laboratories that are not available in endemic areas. The most recent outbreak was in 2019, in which health-care professionals were infected and is recognized as the first outbreak in La Paz department, Bolivia, a place where no prior cases had been reported. In addition, as tourism and travelling increase in Bolivia, along with ecological practices that could represent a risk for acquiring BHF, travelers could be infected, develop the disease, and be a diagnostic challenge in non endemic countries. No vaccines or antiviral therapies are available and approved for human use. Control measures are focused on peridomicile rodent population eradication which demonstrated efficacy in reducing cases during the first outbreaks.
Topics: Arenaviruses, New World; Bolivia; Disease Outbreaks; Hemorrhagic Fever, American; Humans
PubMed: 33640478
DOI: 10.1016/j.tmaid.2021.102001 -
The Journal of Experimental Medicine Oct 2022Recent studies have defined a novel population of PD-1+ TCF-1+ stem-like CD8 T cells in chronic infections and cancer. These quiescent cells reside in lymphoid tissues,...
Recent studies have defined a novel population of PD-1+ TCF-1+ stem-like CD8 T cells in chronic infections and cancer. These quiescent cells reside in lymphoid tissues, are critical for maintaining the CD8 T cell response under conditions of persistent antigen, and provide the proliferative burst after PD-1 blockade. Here we examined the role of TGF-β in regulating the differentiation of virus-specific CD8 T cells during chronic LCMV infection of mice. We found that TGF-β signaling was not essential for the generation of the stem-like CD8 T cells but was critical for maintaining the stem-like state and quiescence of these cells. TGF-β regulated the unique transcriptional program of the stem-like subset, including upregulation of inhibitory receptors specifically expressed on these cells. TGF-β also promoted the terminal differentiation of exhausted CD8 T cells by suppressing the effector-associated program. Together, the absence of TGF-β signaling resulted in significantly increased accumulation of effector-like CD8 T cells. These findings have implications for immunotherapies in general and especially for T cell therapy against chronic infections and cancer.
Topics: Animals; CD8-Positive T-Lymphocytes; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice; Neoplasms; Persistent Infection; Programmed Cell Death 1 Receptor; Transforming Growth Factor beta
PubMed: 35980386
DOI: 10.1084/jem.20211574 -
Viruses Jul 2016Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose an important public health problem in their endemic regions. To date, no Food and Drug... (Review)
Review
Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose an important public health problem in their endemic regions. To date, no Food and Drug Administration (FDA)-licensed vaccines are available to combat human arenavirus infections, and current anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetic approaches has provided investigators with a novel and powerful approach for the study of arenavirus biology including virus-host interactions underlying arenavirus induced disease. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription, as well as particle assembly and budding. Likewise, it is now feasible to rescue infectious arenaviruses containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis. The use of reverse genetics approaches has also allowed the generation of recombinant arenaviruses expressing additional genes of interest. These advances in arenavirus molecular genetics have also facilitated the implementation of novel screens to identify anti-arenaviral drugs, and the development of novel strategies for the generation of arenavirus live-attenuated vaccines. In this review, we will summarize the current knowledge on reporter-expressing, replicating-competent arenaviruses harboring reporter genes in different locations of the viral genome and their use for studying and understanding arenavirus biology and the identification of anti-arenaviral drugs to combat these important human pathogens.
Topics: Animals; Arenavirus; Genes, Reporter; Humans; Reverse Genetics; Staining and Labeling; Virology; Virus Replication
PubMed: 27447662
DOI: 10.3390/v8070197 -
Voprosy Virusologii 2017Lujo hemorrhagic fever (LHF) is a viral disease accompanied with fever, headache, vomiting, diarrhea, arthralgia, myalgia and numerous signs of hemorrhagic syndrome. LHF... (Review)
Review
Lujo hemorrhagic fever (LHF) is a viral disease accompanied with fever, headache, vomiting, diarrhea, arthralgia, myalgia and numerous signs of hemorrhagic syndrome. LHF causes a clinical syndrome remarkably similar to Lassa hemorrhagic fever. The first case of LHF occurred in Johannesburg, South Africa, in 2008. There was a secondary transmission from the index patient to four healthcare workers. Four of the five patients died. The etiologic agent of LHF is Lujo virus (LUJV) belonging to Arenavirus genus of the Arenaviridae Family. Virus Lujo is the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa during the last 40 years. Data about epidemiology, clinical characteristics and diagnostics of LHF, properties of Lujo virus (according to phylogenetic analysis), and recommended precautions for preventing secondary transmission are considered in this paper.
Topics: Arenaviridae Infections; Hemorrhagic Fevers, Viral; Humans; Lujo virus; Phylogeny; South Africa
PubMed: 29733163
DOI: 10.18821/0507-4088-2017-62-4-149-153