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Best Practice & Research. Clinical... Aug 2020Arboviruses (ARthropods BOrne VIRUSES) are disease-causing viruses transmitted through the bite of hematophagous arthropods, such as mosquitoes and ticks. Among these,... (Review)
Review
Arboviruses (ARthropods BOrne VIRUSES) are disease-causing viruses transmitted through the bite of hematophagous arthropods, such as mosquitoes and ticks. Among these, the alphavirus, genus of the Togaviridae family, is considered the most arthritogenic species, responsible for diseases such as chikungunya fever (CHIK), O'nyong-nyong virus fever, Ross River virus disease, Barmah Forest virus disease, Sindbis virus disease, and Mayaro fever. These arboviral diseases, especially CHIK, have impacted public health in recent decades, leading to devastating epidemics, particularly in developing countries, due to their high potential for chronicity, functional impairment, and great impact on the quality of life. In a similar way, chronic musculoskeletal symptoms have been described in all alphavirus infections. However, CHIK is the best studied. The purpose of this article is to review physiopathology, clinical manifestations, diagnosis, and treatment of alphaviruses, focusing on CHIK and chronic evolution of musculoskeletal symptoms.
Topics: Alphavirus; Alphavirus Infections; Animals; Arboviruses; Fever; Humans; Musculoskeletal Diseases; Quality of Life
PubMed: 32312678
DOI: 10.1016/j.berh.2020.101502 -
Expert Opinion on Biological Therapy Jun 2020: Immunotherapy has been introduced as a modern alternative for the treatment of various cancers, including the stimulation of the immune system by introduction of... (Review)
Review
: Immunotherapy has been introduced as a modern alternative for the treatment of various cancers, including the stimulation of the immune system by introduction of immunostimulatory molecules. Application of viral and non-viral vectors have provided a substantial contribution to improved delivery and expression of these immunostimulators.: Alphavirus vectors, based on Semliki Forest virus, have allowed immunization with self-replicating RNA, recombinant virus particles, and layered DNA/RNA vectors. The attractive features of alphaviruses comprise their broad host range and extreme RNA replication in infected cells resulting in very high recombinant protein expression levels providing enhanced immune responses and an excellent basis for immunotherapy.: Immunization studies in animal tumor models have elicited strong humoral and cellular immune response, have provided prophylactic protection against tumor challenges, and have generated therapeutic efficacy in tumor-bearing animals. Clinical trials have indicated safe use of alphavirus vectors, making them attractive for cancer immunotherapy.
Topics: Adaptive Immunity; Animals; Clinical Trials as Topic; Genetic Vectors; Humans; Immunotherapy; Interleukin-12; Neoplasms; Recombinant Proteins; Semliki forest virus
PubMed: 32050824
DOI: 10.1080/14712598.2020.1727438 -
Cell Reports May 2023Arboviruses are public health threats that cause explosive outbreaks. Major determinants of arbovirus transmission, geographic spread, and pathogenesis are the magnitude...
Arboviruses are public health threats that cause explosive outbreaks. Major determinants of arbovirus transmission, geographic spread, and pathogenesis are the magnitude and duration of viremia in vertebrate hosts. Previously, we determined that multiple alphaviruses are cleared efficiently from murine circulation by the scavenger receptor MARCO (Macrophage receptor with collagenous structure). Here, we define biochemical features on chikungunya (CHIKV), o'nyong 'nyong (ONNV), and Ross River (RRV) viruses required for MARCO-dependent clearance in vivo. In vitro, MARCO expression promotes binding and internalization of CHIKV, ONNV, and RRV via the scavenger receptor cysteine-rich (SRCR) domain. Furthermore, we observe species-specific effects of the MARCO SRCR domain on CHIKV internalization, where those from known amplification hosts fail to promote CHIKV internalization. Consistent with this observation, CHIKV is inefficiently cleared from the circulation of rhesus macaques in contrast with mice. These findings suggest a role for MARCO in determining whether a vertebrate serves as an amplification or dead-end host following CHIKV infection.
Topics: Animals; Mice; Chikungunya virus; Viremia; Macaca mulatta; Chikungunya Fever; Disease Outbreaks; Receptors, Immunologic
PubMed: 37083332
DOI: 10.1016/j.celrep.2023.112418 -
Advances in Virus Research 2021Alphaviruses are positive-strand RNA viruses, typically transmitted by mosquitoes between vertebrate hosts. They encode four essential replication proteins, the... (Review)
Review
Alphaviruses are positive-strand RNA viruses, typically transmitted by mosquitoes between vertebrate hosts. They encode four essential replication proteins, the non-structural proteins nsP1-4, which possess the enzymatic activities of RNA capping, RNA helicase, site-specific protease, ADP-ribosyl removal and RNA polymerase. Alphaviruses have been key models in the study of membrane-associated RNA replication, which is a conserved feature among the positive-strand RNA viruses of animals and plants. We review new structural and functional information on the nsPs and their interaction with host proteins and membranes, as well as with viral RNA sequences. The dodecameric ring structure of nsP1 is likely to be one of the evolutionary innovations that facilitated the success of the progenitors of current positive-strand RNA viruses.
Topics: Alphavirus; Animals; RNA, Viral; Vertebrates; Viral Nonstructural Proteins; Virus Replication
PubMed: 34663497
DOI: 10.1016/bs.aivir.2021.07.003 -
Current Rheumatology Reports Apr 2021Persistent joint pain is a common manifestation of arthropod-borne viral infections and can cause long-term disability. We review the epidemiology, pathophysiology,... (Review)
Review
PURPOSE OF REVIEW
Persistent joint pain is a common manifestation of arthropod-borne viral infections and can cause long-term disability. We review the epidemiology, pathophysiology, diagnosis, and management of arthritogenic alphavirus infection.
RECENT FINDINGS
The global re-emergence of alphaviral outbreaks has led to an increase in virus-induced arthralgia and arthritis. Alphaviruses, including Chikungunya, O'nyong'nyong, Sindbis, Barmah Forest, Ross River, and Mayaro viruses, are associated with acute and/or chronic rheumatic symptoms. Identification of Mxra8 as a viral entry receptor in the alphaviral replication pathway creates opportunities for treatment and prevention. Recent evidence suggesting virus does not persist in synovial fluid during chronic chikungunya infection indicates that immunomodulators may be given safely. The etiology of persistent joint pain after alphavirus infection is still poorly understood. New diagnostic tools along and evidence-based treatment could significantly improve morbidity and long-term disability.
Topics: Alphavirus; Alphavirus Infections; Animals; Arthralgia; Arthritis; Arthropods; Humans
PubMed: 33847834
DOI: 10.1007/s11926-021-00987-y -
International Review of Cell and... 2023Alphaviruses have frequently been engineered for cancer therapy, cancer immunotherapy, and cancer vaccine development. As members of self-replicating RNA viruses,...
Alphaviruses have frequently been engineered for cancer therapy, cancer immunotherapy, and cancer vaccine development. As members of self-replicating RNA viruses, alphaviruses provide high levels of transgene expression through efficient self-amplifying of their RNA genome in host cells. Alphavirus vectors can be used as recombinant viral particles or oncolytic viruses. Alternatively, either naked or nanoparticle-encapsulated RNA and DNA replicons can be utilized. In the context of cancer prevention and treatment, antitumor, cytotoxic and suicide genes have been expressed from alphavirus vectors to provide tumor regression and tumor eradication. Moreover, immunostimulatory genes such as cytokines and chemokines have been used for cancer immunotherapy approaches. Expression of tumor antigens has been applied for cancer vaccine development. Alphavirus vectors has demonstrated tumor regression and even cure in various preclinical animal models. Immunization has elicited strong immune responses and showed protection against challenges with tumor cells in animal models. Several clinical trials have confirmed good safety and tolerability of alphaviruses in cancer patients although therapeutic efficacy will still require optimization.
Topics: Animals; Alphavirus; Genetic Vectors; Immunotherapy; RNA; Neoplasms; Cancer Vaccines
PubMed: 37541722
DOI: 10.1016/bs.ircmb.2023.03.011 -
Travel Medicine and Infectious Disease 2023Chikungunya virus is a mosquito-borne alphavirus, transmitted by Aedes mosquitoes. Humans serve as the primary reservoir. Chikungunya infections typically appear with an... (Review)
Review
BACKGROUND
Chikungunya virus is a mosquito-borne alphavirus, transmitted by Aedes mosquitoes. Humans serve as the primary reservoir. Chikungunya infections typically appear with an abrupt onset of fever, rash, and severe joint pain. Some 40% of cases develop chronic rheumatologic complications that can persist months to years.
OBJECTIVES
To improve precision of risk characterization by analyzing cases of chikungunya by year and by country and depicting this geotemporal distribution in map form.
METHOD
Chikungunya case counts by year were compiled from national or regional health authorities from 2011 to 2022. These data were augmented by published reviews plus the Program for Monitoring Emerging Diseases (ProMED). Country-level distribution was categorized into four groups based on recency and magnitude. Data for India were mapped on a per-state basis.
RESULTS
The global map depicts distribution of chikungunya disease from 2011 through 2022. Most cases are reported in tropical and subtropical areas, but notable exceptions include the northern coast of the Mediterranean Sea. Countries of high recency and frequency include India, Brazil, Sudan, and Thailand. Countries with high frequency, but few cases reported in 2019-22 include many Latin American and Caribbean countries. Subnational foci are discussed in general and mapped for India. The range of Aedes mosquitoes is broader than the geography where chikungunya infection is typically diagnosed.
CONCLUSIONS
These maps help identify geographical regions where residents or travelers are at greatest risk of chikungunya. Once vaccines are licensed to help prevent chikungunya, maps like these can help guide future vaccine decision-making.
Topics: Animals; Humans; Chikungunya Fever; Mosquito Vectors; Chikungunya virus; Aedes; Exanthema
PubMed: 37307983
DOI: 10.1016/j.tmaid.2023.102603 -
The Veterinary Clinics of North... Apr 2023The continued recognition and emergence of alphavirus and flavivirus diseases is a growing veterinary and public health concern. As the global environment continues to... (Review)
Review
The continued recognition and emergence of alphavirus and flavivirus diseases is a growing veterinary and public health concern. As the global environment continues to change, mosquito-borne diseases will continue to evolve and expand. Continued development of readily available vaccines for the prevention of these diseases in humans and animals is essential to controlling epizootics of these diseases. Further research into effective antiviral treatments is also sorely needed. This article describes equine encephalitis viruses with a focus on clinical and public health considerations.
Topics: Animals; Horses; Humans; West Nile virus; Encephalomyelitis, Venezuelan Equine; Public Health; Horse Diseases; Alphavirus
PubMed: 36737290
DOI: 10.1016/j.cveq.2022.11.007 -
Current Topics in Microbiology and... 2022Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has caused both small- and large-scale epidemics of incapacitating musculoskeletal disease across the...
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has caused both small- and large-scale epidemics of incapacitating musculoskeletal disease across the globe. A substantial proportion of infected individuals experience debilitating arthralgia and/or arthritis that can persist in relapsing or continuous forms for months to years, an occurrence that appears independent of viral strain and outbreak location. Due to the lack of CHIKV-specific vaccine or therapeutics, treatment of chronic CHIKV disease is limited to supportive care. Although the epidemiologic and molecular mechanisms that dictate resolution or chronicity of CHIKV disease remain unclear, several risk factors and immunological responses have been implicated in the development of chronic CHIKV disease. Mounting evidence from animal models and limited case studies indicates that chronic disease is likely a result of induced autoimmunity and/or viral persistence in joint-associated tissue. Due to the global spread and explosive, often unpredictable nature of CHIKV epidemics, concerted efforts to obtain a more precise understanding of the development and maintenance of chronic CHIKV disease must be at the forefront of investigative endeavors.
Topics: Animals; Chikungunya Fever; Chikungunya virus; Disease Outbreaks; Humans
PubMed: 30656438
DOI: 10.1007/82_2018_147 -
Advances in Virus Research 2022Alphaviruses are a large group (>30 species) of enveloped, positive-strand RNA viruses. The re-emergence of mosquito-transmitted alphaviruses associated with human... (Review)
Review
Alphaviruses are a large group (>30 species) of enveloped, positive-strand RNA viruses. The re-emergence of mosquito-transmitted alphaviruses associated with human diseases ranging from severe and potentially fatal neurological disease to chronic arthritic disease highlights the need to understand the biology and pathogenesis of alphaviruses. Here, we review the development and use of animal models of alphavirus transmission and human disease, and discuss areas for continued refinement of these models including possible avenues for future investigation.
Topics: Animals; Humans; Alphavirus Infections; Alphavirus; Disease Models, Animal
PubMed: 36307168
DOI: 10.1016/bs.aivir.2022.07.001