Dataset Information

Alphavirus Virulence Determinants.

ABSTRACT: Alphaviruses are important pathogens that continue to cause outbreaks of disease in humans and animals worldwide. Diseases caused by alphavirus infections include acute symptoms of fever, rash, and nausea as well as chronic arthritis and severe-to-fatal conditions including myocarditis and encephalitis. Despite their prevalence and the significant public health threat they pose, there are currently no effective antiviral treatments or vaccines against alphaviruses. Various genetic determinants of alphavirus virulence, including genomic RNA elements and specific protein residues and domains, have been described by researchers to play key roles in the development of disease, the immune response to infection, and virus transmissibility. Here, we focus on the determinants that are currently described in the literature. Understanding how these molecular determinants shape viral infections can lead to new strategies for the development of therapies and vaccines to combat these viruses.

SUBMITTER: Rangel MV

PROVIDER: S-EPMC8401390 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alphavirus Virulence Determinants.

Rangel Margarita V MV Stapleford Kenneth A KA

Pathogens (Basel, Switzerland) 20210803 8

Alphaviruses are important pathogens that continue to cause outbreaks of disease in humans and animals worldwide. Diseases caused by alphavirus infections include acute symptoms of fever, rash, and nausea as well as chronic arthritis and severe-to-fatal conditions including myocarditis and encephalitis. Despite their prevalence and the significant public health threat they pose, there are currently no effective antiviral treatments or vaccines against alphaviruses. Various genetic determinants o ...[more]

PMID: 34451445

Similar Datasets

Project description:The alphavirus chikungunya virus (CHIKV) is a serious human pathogen that can cause large-scale epidemics characterized by fever and joint pain and often resulting in chronic arthritis. Infection by alphaviruses including CHIKV and the closely related Semliki Forest virus (SFV) can induce the formation of filopodia-like intercellular long extensions (ILEs). ILEs emanate from an infected cell, stably attach to a neighboring cell, and mediate cell-to-cell viral transmission that is resistant to neutralizing antibodies. However, our mechanistic understanding of ILE formation is limited, and the potential contribution of ILEs to CHIKV virulence or human CHIKV infection is unknown. Here, we used well-characterized virus mutants and monoclonal antibodies with known epitopes to dissect the virus requirements for ILE formation. Our results showed that both the viral E2 and E1 envelope proteins were required for ILE formation, while viral proteins 6K and transframe, and cytoplasmic nucleocapsid formation were dispensable. A subset of CHIKV monoclonal antibodies reduced ILE formation by masking specific regions particularly on the E2 A domain. Studies of the viral proteins from different CHIKV strains showed that ILE formation is conserved across the four major CHIKV lineages. Sera from convalescent human CHIKV patients inhibited ILE formation in cell culture, providing the first evidence for ILE inhibitory antibody production during human CHIKV infections.IMPORTANCEChikungunya virus (CHIKV) infections can cause severe fever and long-lasting joint pain in humans. CHIKV is disseminated by mosquitoes and is now found world-wide, including in the Americas, Asia, and Africa. In cultured cells, CHIKV can induce the formation of long intercellular extensions that can transmit virus to another cell. However, our understanding of the formation of extensions and their importance in human CHIKV infection is limited. We here identified viral protein requirements for extension formation. We demonstrated that specific monoclonal antibodies against the virus envelope proteins or sera from human CHIKV patients can inhibit extension formation. Our data highlight the importance of evaluation of extension formation in the context of human CHIKV infection.

Project description:Taxonomic relationshipsCucumber mosaic virus (CMV) is the type species of the genus Cucumovirus in the family Bromoviridae, which also encompasses the Peanut stunt virus (PSV) and the Tomato aspermy virus (TAV). Nucleotide sequence similarity among these three cucumoviruses is 60%-65%. CMV strains are divided into three subgroups, IA, IB and II, based on the sequence of the 5' untranslated region of the genomic RNA 3. Overall nucleotide sequence similarity among CMV strains is approximately 70%-98%. GEOGRAPHICAL DISTRIBUTION, HOST RANGE AND SYMPTOMATOLOGY: CMV is distributed worldwide, primarily in temperate to tropical climate zones. CMV infects more than 1200 species of 100 plant families, including monocot and dicot plants. Symptoms caused by CMV infection vary with the host species and/or CMV strain, and include mosaic, stunt, chlorosis, dwarfing, leaf malformation and systemic necrosis. CMV disease is spread primarily by aphid transmission in a nonpersistent manner.Physical propertiesIn tobacco sap, the thermal inactivation point of the viral infectivity is approximately 70 °C (10 min), the dilution end-point is approximately 10(-4) and viral infectivity is lost after a few days of exposure to 20 °C. Viral infectivity can be retained in freeze-dried tissues and in the form of virions purified using 5 mm sodium borate, 0.5 mm ethylenediaminetetraacetic acid and 50% glycerol (pH 9.0) at -20 °C. CMV particles are isometric, approximately 28-30 nm in diameter and are composed of 180 capsid subunits arranged in pentamer-hexamer clusters with T= 3 symmetry. The sedimentation coefficient (s(20) ,(w) ) is c. 98 S and the particle weight is (5.8-6.7) × 10(6) Da. The virions contain 18% RNA. The RNA-protein interactions that stabilize the CMV virions are readily disrupted by sodium dodecylsulphate or neutral chloride salts. GENOMIC PROPERTIES: The genomic RNAs are single-stranded messenger sense RNAs with 5' cap and 3' tRNA-like structures containing at least five open reading frames. The viral RNA consists of three genomic RNAs, RNA 1 (c. 3.3 kb), RNA 2 (c. 3.0 kb) and RNA 3 (c. 2.2 kb), and two subgenomic RNAs, RNA 4 (c. 1.0 kb) and RNA 4A (c. 0.7 kb). The 3' untranslated regions are conserved across all viral RNAs. CMV is often accompanied by satellite, noncoding, small, linear RNA that is nonhomologous to the helper CMV.

Dataset Information

Alphavirus Virulence Determinants.

Publications

Alphavirus Virulence Determinants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets