Arthritogenic alphaviruses: epidemiological and clinical perspective on emerging arboviruses.

Mosquito-borne viruses, or arboviruses, have been part of the infectious disease landscape for centuries, and are often, but not exclusively, endemic to equatorial and subtropical regions of the world. The past two decades saw the re-emergence of arthritogenic alphaviruses, a genus of arboviruses that includes several members that cause severe arthritic disease. Recent outbreaks further highlight the substantial public health burden caused by these viruses. Arthritogenic alphaviruses are often reported in the context of focused outbreaks in specific regions (eg, Caribbean, southeast Asia, and Indian Ocean) and cause debilitating acute disease that can extend to chronic manifestations for years after infection. These viruses are classified among several antigenic complexes, span a range of hosts and mosquito vectors, and can be distributed along specific geographical locations. In this Review, we highlight key features of alphaviruses that are known to cause arthritic disease in humans and outline the present findings pertaining to classification, immunogenicity, pathogenesis, and experimental approaches aimed at limiting disease manifestations. Although the most prominent alphavirus outbreaks in the past 15 years featured chikungunya virus, and a large body of work has been dedicated to understanding chikungunya disease mechanisms, this Review will instead focus on other arthritogenic alphaviruses that have been identified globally and provide a comprehensive appraisal of present and future research directions.

Neurological manifestations of pediatric arboviral infections in the Americas.

Dengue, Zika, Chikungunya and yellow fever viruses are arboviruses transmitted by the mosquito Aedes aegypti. These viruses exhibit marked neurotropism but have rarely been studied. Here, we conduct an integrative review of the neurological manifestations caused by these arboviruses in the pediatric population. Data on patients under 18 years of age were extracted from literature databases. The most frequently reported neurological manifestations were encephalitis, meningitis, seizures, hypotonia, paresis, and behavioral changes. This review highlights the importance of accurately diagnosing these arboviral infections in children and adolescents with neurological manifestations.

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors.

RNA interference- and genome editing-based screening platforms have been widely used to identify host cell factors that restrict virus replication. However, these screens are typically conducted in cells that are naturally permissive to the viral pathogen under study. Therefore, the robust replication of viruses in control conditions may limit the dynamic range of these screens. Furthermore, these screens may be unable to easily identify cellular defense pathways that restrict virus replication if the virus is well-adapted to the host and capable of countering antiviral defenses. In this article, we describe a new paradigm for exploring virus-host interactions through the use of screens that center on naturally abortive infections by arboviruses such as vesicular stomatitis virus (VSV). Despite the ability of VSV to replicate in a wide range of dipteran insect and mammalian hosts, VSV undergoes a post-entry, abortive infection in a variety of cell lines derived from lepidopteran insects, such as the gypsy moth (Lymantria dispar). However, these abortive VSV infections can be "rescued" when host cell antiviral defenses are compromised. We describe how VSV strains encoding convenient reporter genes and restrictive L. dispar cell lines can be paired to set-up screens to identify host factors involved in arbovirus restriction. Furthermore, we also show the utility of these screening tools in the identification of virally encoded factors that rescue VSV replication during coinfection or through ectopic expression, including those encoded by mammalian viruses. The natural restriction of VSV replication in L. dispar cells provides a high signal-to-noise ratio when screening for the conditions that promote VSV rescue, thus enabling the use of simplistic luminescence- and fluorescence-based assays to monitor the changes in VSV replication. These methodologies are valuable for understanding the interplay between host antiviral responses and viral immune evasion factors.

Taking a bite out of nutrition and arbovirus infection.

Nutrition is a key factor in host-pathogen defense. Malnutrition can increase both host susceptibility and severity of infection through a number of pathways, and infection itself can promote nutritional deterioration and further susceptibility. Nutritional status can also strongly influence response to vaccination or therapeutic pharmaceuticals. Arthropod-borne viruses (arboviruses) have a long history of infecting humans, resulting in regular pandemics as well as an increasing frequency of autochthonous transmission. Interestingly, aside from host-related factors, nutrition could also play a role in the competence of vectors required for transmission of these viruses. Nutritional status of the host and vector could even influence viral evolution itself. Therefore, it is vital to understand the role of nutrition in the arbovirus lifecycle. This Review will focus on nutritional factors that could influence susceptibility and severity of infection in the host, response to prophylactic and therapeutic strategies, vector competence, and viral evolution.

Infections of the developing world.

Access to critical care is rapidly growing in areas of the world where it was previously nonexistent and where infectious diseases often comprise the largest disease burden. Additionally, with crowding, mass migrations, and air travel, infectious diseases previously geographically confined are quickly spread across the planet, often in shorter time frames than disease incubation periods. Hence, critical care practitioners must be familiar with infectious diseases previously confined to the developing world. This article reviews selected tropical diseases that are seen in diverse locales and often require critical care services.

North American encephalitic arboviruses.

Arboviruses continue to be a major cause of encephalitis in North America, and West Nile virus neuroinvasive disease is now the dominant cause of encephalitis. Transmission to humans of North American arboviruses occurs by infected mosquitoes or ticks. Most infections are asymptomatic or produce a flulike illness. Rapid serum or cerebrospinal fluid IgM antibody capture ELISA assays are available to diagnosis the acute infection for all North American arboviruses. Unfortunately, no antiviral drugs are approved for the treatment of arbovirus infection and current therapy is supportive.

The host complement system and arbovirus pathogenesis.

Arthropod-borne viruses (arboviruses) are a significant cause of human diseases worldwide. Interactions between these viruses and the innate immune system play a major role in determining the outcome of disease. The complement system is particularly important in this process as activation of complement can contribute to both host defense as well as injury to host tissues. This review focuses on the increasing evidence that the complement system plays key roles in both protective and pathologic outcomes of arbovirus infection.

Arboviruses and their vectors in the Pacific--status report.

Three arboviruses have already caused epidemics in various Pacific Island countries and territories, and currently represent a direct threat to public health. The diseases concerned are all mosquito-borne and should be kept under careful surveillance. Dengue fever, which is a worldwide major public health problem, is mainly transmitted in the Pacific by the Aedes aegypti vector but also by other mosquitoes of this genus with varying ranges. Epidemic polyarthritis due to the Ross River virus is endemic in Australia. At least one major epidemic has occurred in the Pacific where various vector mosquito species occur. Japanese encephalitis is a zoonosis that can be transmitted to humans by mosquitoes of the genus Culex. Its area of distribution in Asia is expanding and the possibility of fresh incursions into the region should be borne in mind. This paper reviews the situation regarding these diseases in the Pacific and provides information on the way they are transmitted as well as on the biology of the mosquito vectors.

The global emergence/resurgence of arboviral diseases as public health problems.

During the past 20 years there has been a dramatic resurgence or emergence of epidemic arboviral diseases affecting both humans and domestic animals. These epidemics have been caused primarily by viruses thought to be under control such as dengue, Japanese encephalitis, yellow fever, and Venezuelan equine encephalitis, or viruses that have expanded their geographic distribution such as West Nile and Rift Valley fever. Several of these viruses are presented as case studies to illustrate the changing epidemiology. The factors responsible for the dramatic resurgence of arboviral diseases in the waning years of the 20th century are discussed, as is the need for rebuilding the public health infrastructure to deal with epidemic vector-borne diseases in the 21st century.

[Arbovirus infections. From virus, mosquitoes, animals and humans]. / Arboviroses. Des virus, des moustiques, des animaux et des hommes.

Arboviruses occur throughout the world in plants and animals: reptiles, birds and mammals including man. These relatively recent RNA-containing viruses have great evolutionary potential and are a major cause of epidemics. Arboviruses exhibit a dual life cycle involving continual transmission to and from the vertebrate host and arthropod vector which ingests or inoculates the agent during blood meals. Agents belong to many different viral families and represent an important source of emerging diseases. Because of the mode of transmission is vectorial, spread can enhanced by man-made changes in the ecosystem. This risk is often underestimated. The population explosion provides a great opportunity for the progression of these arboviruses.

Epidemiology of arboviral infections.

OBJECTIVE: To review the current state of knowledge regarding the epidemiology of arboviruses. DATA SOURCES: Computerized literature searches, identification of papers through review of article bibliographies, and Yale Arbovirus Research Unit, USA. STUDY SELECTION: Articles documenting research pertaining to the epidemiology of arboviruses with emphasis on factors that increase or decrease the spread of these infections. DATA EXTRACTION: The review articles were extracted independently by the authors. DATA SYNTHESIS: Arboviral infections are a global health problem accounting for significant morbidity and mortality in human and animal populations. They belong to the families Togaviridae, Flaviviridae, Bunyaviridae, Reoviridae, and Rhabdoviridae, and are transmitted to humans and domestic animals by the bite of infected arthropods. Rodents and birds are significant vertebrate hosts, while humans are usually not involved in the maintenance and spread of most arboviruses. Ecologic changes and human behavior are important in the spread of these infections. Clinical features range from mild fevers to fatal encephalitis. Surveillance, immunization, and vector control are important methods of prevention. CONCLUSION: It appears that the distribution and spread of arboviruses is greatly influenced by human behavior and ecologic changes in the environment. Awareness regarding these and other factors, such as travel history, history of bites of arthropods, concurrent epidemic pattern in the community, and knowledge of surveillance data are useful ways of identifying these infections. Future research may be directed toward methodical search for new arboviruses and their relation to human and animal disease.

In vivo reassortment of Thogoto virus (a tick-borne influenza-like virus) following oral infection of Rhipicephalus appendiculatus ticks.

Arboviruses with segmented genomes have the potential to reassort in both their vertebrate hosts and arthropod vectors. Reassortment of Thogoto virus, a tick-borne orthomyxo-like virus, has been demonstrated following dual infection of hamsters by temperature-sensitive mutants. To investigate whether similar events can occur in ticks, Rhipicephalus appendiculatus larvae and nymphs were dually infected by interrupted feeding on viraemic hamsters. Wild-type reassortant virus was isolated from the ticks 12 to 15 days after engorgement. Following moulting, nymphs and adults transmitted reassortant virus to uninfected hamsters. This is the first reported evidence that a tick-borne arbovirus can reassort in vivo in a naturally infected arthropod vector. The relative roles of vector and vertebrate host in generating and perpetuating reassortant viruses in nature are discussed.

Effect of Sindbis birus infection on survival of mice in the cold.

Mice infected with 10(9) plaque-forming units (PFU) of Sindbis virus 9 h prior to exposure to cold (5 degrees C) died more rapidly after entering the new environment than saline-injected control mice. The early deaths occurred in animals singly housed without bedding and only when food was withheld. Because deaths could be prevented by providing the infected animals with food, it was concluded that metabolic alteractions resulting from the virus infection were responsible for the deaths. As evidence, corticosteroid-inducible hepatic enzymes did not respond to hydrocortisone administration in virus-infected mice housed at 5 degrees C. Phosphoenolpyruvate carboxykinase (PEPCK) (EC 4.1.1.32) was induced significantly in control mice held at 5 degrees C for 5 h, but failed to induce in infected mice in the cold. Tryptophan oxygenase (TO) (EC 1.13.11.11) activity was also induced in control mice at 5 degrees C, but was too low to be measured in livers of all infected mice including those exposed to cold. The conclusion that Sindbis virus-infected mice were unable to make the metabolic adjustments required for survival at 5 degrees C was further indicated by severe hypoglycemia and rapid drop in rectal temperature that occurred in infected mice after 5 h in the cold.