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MDV-like endogenous viral elements act as immune rheostats in Aedes cells by modulating defensin A-mediated responses to arboviruses.

Mosquito cell lines are essential tools for arbovirus research. Endogenous viral elements (EVEs) are prevalent in mosquito genomes, yet their functional effects on host immune responses remain unclear, potentially complicating experimental interpretations. In this study, we systematically characterized endogenous mosquito densovirus-like elements (EMLs) within the Aedes aegypti Aag2 cell line and found that these endogenous EMLs are transcriptionally active but translationally defective. The silencing of EML transcripts significantly diminished the replication of Zika virus (ZIKV), Japanese encephalitis virus (JEV), and chikungunya virus (CHIKV), while transiently increasing dengue virus 2 (DENV-2), thereby indicating a virus-dependent regulatory mechanism. Mechanistically, RNA sequencing after EML interference, alongside plasmid-based mimic expression, demonstrated that EML transcripts downregulate defensin A, an antimicrobial peptide produced by mosquitoes. Functional assays using synthetic defensin A showed that this peptide differentially regulates arboviral infection. Binding assays and structural modeling further supported its interaction with viral envelope proteins, while stage-restricted infection assays revealed distinct stages of action: defensin A enhanced adsorption of ZIKV, JEV, and CHIKV, but did not promote DENV-2 adsorption or entry, and instead reduced DENV-2 RNA accumulation at the post-entry replication stage. Our findings highlight a previously unrecognized role of densovirus-derived EVEs in mosquito innate immunity, extending their functional scope from the well-established PIWI-interacting RNA-mediated antiviral defense to the regulation of antimicrobial peptide-associated immune pathways. These findings emphasize the necessity of accounting for EVE activity when analyzing data derived from mosquito cell lines, and suggest that related EVE-mediated immune regulation may contribute to arbovirus dynamics in mosquitoes.IMPORTANCEMosquito-borne viruses such as dengue, Zika, Japanese encephalitis, and chikungunya continue to threaten human health worldwide. Laboratory studies often use Aedes aegypti cell lines to investigate how these viruses interact with their mosquito hosts. Here, we show that the genomes of these cells contain endogenous viral elements derived from mosquito densoviruses. Far from being inert fossils, these sequences are transcriptionally active and regulate mosquito immunity by suppressing the antimicrobial peptide defensin A. This immune modulation influences the replication of different arboviruses in opposite ways, enhancing some while restricting others. Our findings reveal that integrated viral elements can shape the outcome of arbovirus infection, with important implications for interpreting mosquito cell culture experiments and for evaluating endogenous viral element-mediated immune regulation in mosquito-virus interactions.

Aag2 cell↗

Human sentinels for arbovirus surveillance and regional risk classification in South Australia.

OBJECTIVES: To assess the use of human sentinels to monitor arbovirus activity in South Australia and to use age-specific seroprevalence data from the same sentinels to classify regions according to risk from Ross River virus (RRV). METHODS: Between 1 January 1992 and 15 August 1992, 4776 serum samples were obtained from Red Cross blood donors in the State. All sera were tested for the presence of total antibody (IgA, IgG and IgM) by indirect enzyme immunoassay. To test for recent infection, positive sera were further tested for IgA and IgM specific antibody to Ross River virus with a view to initiating public health interventions if necessary. The age, sex and postcode of residence of each donor were also recorded for seroepidemiological studies. RESULTS: Of the 4776 sera, 2952 were tested to the end of May (the end of the arbovirus season in South Australia). There was evidence of RRV infection in 248 sera (8.4%) but none had serological markers consistent with recent infection. The arbovirus season was considered non-epidemic, and no reactive public health interventions were introduced. Analysis of age-specific seroprevalence by post-code in the full bank of 4776 sera indicated that the Riverland is endemic for RRV, the Murray Mallee and Upper South East epidemic for RRV, and the remaining regions of the State at variable risk, depending on their proximity to these regions. CONCLUSIONS: The ongoing use of human sentinels is a new public health surveillance system for this disease. In the first year of operation of this surveillance system, a suboptimal number of sera was collected from some areas, and sera were tested only for RRV. However, the number of sera tested could easily be increased, as could the range of arboviruses covered by the testing.

Adult↗

Non-viraemic transmission of tick-borne encephalitis virus: a mechanism for arbovirus survival in nature.

The vectors of arthropod-borne viruses (arboviruses) become infected by feeding on the viraemic blood of an infected animal. This theory is based on transmission studies involving artificial infection of vertebrate hosts by syringe inoculation. To reproduce natural conditions of virus transmission, infected and uninfected vectors (ticks) of tick-borne encephalitis virus, the most important arbovirus in Europe, were allowed to feed together on uninfected wild vertebrate hosts. The greatest numbers of infected ticks were obtained from susceptible host species that had undetectable or very low levels of viraemia. The results suggest that 'nonviremic transmission' is an important mechanism for the survival of certain arboviruses in nature.

Animals↗

Arbovirus isolations from, and serological studies on, wild and domestic vertebrates from Kano Plain, Kenya.

Arbovirus infection and presence of haemagglutination-inhibiting antibodies in small mammals, birds and livestock were examined over a period of five years on the Kano Plain in western Kenya. Eleven isolations were made from mammals and birds. The viruses were identified as Arumowot and Germiston while three different agents could not be shown to be related to 188 African arboviruses. Prevalence of antibodies against arboviruses suspected of occurring in the area was generally low.

Animal Population Groups↗

Biological transmission of arboviruses: reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends.

Among animal viruses, arboviruses are unique in that they depend on arthropod vectors for transmission. Field research and laboratory investigations related to the three components of this unique mode of transmission, virus, vector, and vertebrate host, have produced an enormous amount of valuable information that may be found in numerous publications. However, despite many reviews on specific viruses, diseases, or interests, a systematic approach to organizing the available information on all facets of biological transmission and then to interpret it in the context of the evolutionary process has not been attempted before. Such an attempt in this review clearly demonstrates tremendous progress made worldwide to characterize the viruses, to comprehend disease transmission and pathogenesis, and to understand the biology of vectors and their role in transmission. The rapid progress in molecular biologic techniques also helped resolve many virologic puzzles and yielded highly valuable data hitherto unavailable, such as characterization of virus receptors, the genetic basis of vertebrate resistance to viral infection, and phylogenetic evidence of the history of host range shifts in arboviruses. However, glaring gaps in knowledge of many critical subjects, such as the mechanism of viral persistence and the existence of vertebrate reservoirs, are still evident. Furthermore, with the accumulated data, new questions were raised, such as evolutionary directions of virus virulence and of host range. Although many fundamental questions on the evolution of this unique mode of transmission remained unresolved in the absence of a fossil record, available observations for arboviruses and the information derived from studies in other fields of the biological sciences suggested convergent evolution as a plausible process. Overall, discussion of the diverse range of theories proposed and observations made by many investigators was found to be highly valuable for sorting out the possible mechanism(s) of the emergence of arboviral diseases.

Animals↗

Relationship between the prevalence of antibodies to arbovirus and hepatitis B virus in the Vale do Ribeira region, Brazil.

280 students, between 6 and 14 years old, residents in the Iguape county, southern coast of the State of São Paulo, were studied in order to identify the existence of a possible association between the prevalence of specific antibodies to the hepatitis B virus and the exposure to haematophagous mosquitoes, evaluated indirectly through the prevalence of antibodies to 17 arboviruses isolated in Brazil. The children were from 4 areas with different topographical characteristics: 89 of the children were from the urban zone of the town of Iguape, 89 were from the peri-urban zone, 30 were from the rural area with extensive banana plantations, and 72 were from the jungle zone. Previous studies had shown significantly higher prevalence of antibodies to different arboviruses in the cultivated zone and the jungle zone, when compared to the urban and peri-urban zones of Iguape. The detection of antibodies to the HBV surface antigen (HBs Ag) was done through the radioimmunoassay (Ausab, Abbott Laboratory). The cases considered positive were confirmed through the presence of anti-core HBV antibodies (anti-HBc-EIA Roche). A significantly higher prevalence of anti-HBV antibodies was observed in children from the jungle zone (26/72 = 36.1%) when compared to those from the urban zone (5/89 = 5.6%), peri-urban (6/89 = 6.7%) or from the cultivated zone (0/30 = 0%). The result suggest the existence of a common factor in the dissemination of the arboviruses and the hepatitis B virus, supporting the hypothesis that mosquitoes may play an important role in the HBV transmission in tropical forested region.

Adolescent↗

Inadequate management of natural ecosystem in the Brazilian Amazon region results in the emergence and reemergence of arboviruses.

A total of 187 different species of arboviruses and other viruses in vertebrates were identified at the Evandro Chagas Institute (IEC) from 1954 to 1998, among more than 10,000 arbovirus strains isolated from humans, hematophagous insects, and wild and sentinel vertebrates. Despite intensive studies in the Brazilian Amazon region, especially in Pará State, very little is known about most of these viruses, except for information on date, time, source, and method of isolation, as well as their capacity to infect laboratory animals. This paper reviews ecological and epidemiological data and analyzes the impact of vector and host population changes on various viruses as a result of profound changes in the natural environment. Deforestation, mining, dam and highway construction, human colonization, and urbanization were the main manmade environmental changes associated with the emergence and/or reemergence of relevant arboviruses, including some known pathogens for humans.

Animals↗

Initiating arbovirus surveillance in Arkansas, 2001.

Migratory birds could introduce West Nile (WN) virus to Arkansas. The purpose of this study was to establish a cooperative arbovirus surveillance program to monitor mosquitoes and birds in Arkansas for arboviruses. Our objectives were to: 1) perform routine, multicounty collections of mosquitoes and test them for eastern equine encephalitis, St. Louis encephalitis, and WN viruses; and 2) conduct passive surveillance by testing dead wild birds for WN virus. Arbovirus surveillance was organized by the Arkansas Department of Health, University of Arkansas, and Vector Disease Control Incorporated. None of the 14,560 mosquitoes (425 pools) tested were virus positive. Two hundred forty-two dead birds from 62 counties were tested for WN virus. Four blue jays in three counties were positive. These infections are the first reported incidences of WN virus in Arkansas. Sera from five horses with suspected encephalitis all tested negative for WN, eastern equine encephalitis, and western equine encephalitis viruses.

Animals↗

Arbovirus surveillance in six states during 1972.

A virus surveillance project was established and maintained during 1972 along 10 major river drainages in six states. Mosquitoes, biting flies, and blood specimens from sentinel equines were collected during 83 field trip visits to 141 arthropod collecting sites and 22 sentinel locations from April into December 1972. There were 173,074 mosquitoes tested and 303 arboviruses isolated from 11 of 41 species. From 13,388 biting flies tested, 8 arbovirus isolations were obtained in 1 of 5 species. There was no isolation of Venezuelan equine encephalitis (VEE) virus. Western equine encephalitis (WEE) virus isolates were the most numerous and were followed by Turlock, St. Louis encephalitis, Hart Park, California encephalitis, and Bunyamwera (BUN) group viruses. The first isolation of WEE from the mosquito Cullex (Mel). erraticus is reported, as is the extension of the ranges for Buttonwillow virus from California to New Mexico and Texas. Also a single isolation of the BUN group from Culicoides variipennis extends the range of this virus-vector relationship from California to Texas. New distribution records for mosquito species previously unreported for Arizona, Louisana, New Mexico, and Oklahoma are reported. The sentinel burros detected WEE serologic conversions at two sites in New Mexico and at one in Texas. The surveillance project provided state and federal officials with current information on the status of arbovirus activity, including the absence of VEE activity during 1972, and it demonstrated the existence of the potential for WEE epizootics and epidemics throughout a wide geographic area of the Western United States.

Animals↗

Epidemiological investigation for arboviruses in Jamaica, West Indies.

Arbovirus investigation in Jamaica was undertaken between 1960 and 1975. Serological studies showed that antibodies to dengue type virus and St. Louis encephalitis virus (SLE) were prevalent throughout the island for several years. In urban communities, the incidence of dengue antibody was higher than for SLE; however, in children under 10 years of age antibody to both viruses was rarely present. In rural areas, SLE was prevalent in adults and children. This virus was isolated fom Culex nigripalpus (mosquitoes) and from a nestling Mockingbird, Mimus polyglottos, in the same rural area. Dengue type 3 and type 4 were isolated from the sera of patients in an urban area, during two epidemic periods, 1963 and 1968. No other group B arbovirus was encountered on the island. Group A arbovirus was virtually absent prior to the eastern equine encephalomyelitis outbreak of 1962. That virus was isolated from brain tissue of humans and equines. Two strains of Cache Valley virus from mosquitoes, Anopheles grabhami, one strain from Aedes taeniorhynchus, and a strain of Wad Medani virus from a tick, Amblyomma cajenense, were also isolated.

Adolescent↗

Sylvatic transmission of arboviruses among Bornean orangutans.

Wild populations of nonhuman primates live in regions of sylvatic arbovirus transmission. To assess the status of arbovirus transmission in Bornean forests and the susceptibility of wild orangutans to arboviral infection, blood samples of wild orangutans, semi-captive orangutans, and humans were examined. Samples were tested by plaque reduction neutralization test for antibodies to viruses representing three families (Flaviviridae, Alphaviridae, and Bunyaviridae), including dengue-2, Japanese encephalitis, Zika, Langat, Tembusu, Sindbis, Chikungunya, and Batai viruses. Both wild and semi-captive orangutan groups as well as local human populations showed serologic evidence of arbovirus infection. The presence of neutralizing antibodies among wild orangutans strongly suggests the existence of sylvatic cycles for dengue, Japanese encephalitis, and sindbis viruses in North Borneo. The present study demonstrates that orangutans are susceptible to arboviralinfections in the wild, although the impact of arboviral infections on this endangered ape remain unknown.

Animals↗

Transovarial transmission of arboviruses by mosquitoes: a review.

One interesting aspect of mosquito-borne arboviruses is their endemic persistence, espeically during adverse climatic conditions in the temperate zones. The hypothesis that transovarial transmission of alpha- and flaviviruses by their respective mosquito vectors could serve as an overwintering mechanism has been proposed; however, experimental data in support of this hypothesis are not very convincing. Recently, some of the California encephalitis group arboviruses have been shown to be transmitted transovarially by Aedes species mosquitoes, and studies indicate that this mechanism contributes to the natural maintenance cycle of these viruses. Finally, consideration is given to the possibility that transovarial transmission may be unique to the California encephalitis group arboviruses and may be related to their association with a vector that overwinters in the egg stage of its life cycle.

Aedes↗

Short report: detection probability of arbovirus infection in mosquito populations.

An important component of arbovirus surveillance is monitoring the vector for presence of the pathogen. Intervention and preventive programs need early detection of arboviral activity in mosquito populations. In this report, we examine the factors affecting the probability of detection of mosquito infections. Since arbovirus infection rates in mosquito populations are very low, observations of zero-infected mosquito samples are common. Using statistical models, we describe methods to estimate the probability of detection and upper bounds of confidence intervals of mosquito infection rates as measures of confidence for observations of zero infection. Our results show that detection of low levels of mosquito infections requires large samples (greater than 1,600 individuals) for a high probability (0.8) of detection. Due to focal transmission of arboviruses, grouping samples over different sampling sites and times is often inappropriate for detection of mosquito infection. We emphasize sample size as a key determinant in detection of mosquito infections and recommend intensified entomologic surveys at sentinel sites to detect arboviral activity.

Animals↗

International arbovirus research.

International cooperation in arbovirus research became increasingly prominent shortly after it was found in the early 1940's, that antigenic relationships existed among certain viruses isolated in different areas of thw world. The interest of a number of scientists and of a private organization led to the establishment of an international information exchange and to the preparation of an international catalogue of arboviruses including certain other viruses of vertebrates. International cooperation was fostered by the interest taken in these agents by the World Health Organization and the creation by this agency of an international net of collaborating laboratories with assigned areas of the world. A number of recent problems have been revealed and solved, or partly solved by this international effort, among which are questions relating to: the Marburg agent disease, the existence of an antigenic relationship between rabies virus and some arboviruses, aspects of the ecology or viruses in the California, Uukuniemi and Kemerovo groups, as well as several unanticipated antigenic relationships among viruses. Numerous questions still remain the solution of which might be expedited by continued and increased cooperative international effort such as overwintering or survival of viruses under unfavorable circumstances, pathogenic potential for man and domestic animals of certain viruses, role on chronic illnesses, establishment of the etiology of certain diseases and investigations of the basic properties of viruses, particularly of the Bunyaviridae.

Animals↗

[Radioimmunologic analysis for the rapid diagnosis of arbovirus infections].

The employment of radioimmunoassay (RIA) allows arbovirus infections to be diagnosed at an early stage of the illness. In the present study the best variant of RIA was determined with regard to its practical use in rapid diagnosis of some arbovirus infections and its superiority over CFT, HI, IHA, IF. The method was shown to be highly specific and sensitive for qualitative studies of specimens from natural foci of arboviruses and for timely diagnosis of human illnesses.

Antibodies, Viral↗

[Arboviruses in Iran (author's transl)].

During an entomological survey conducted in april-june 1978 in the province of Khorassan in the eastern part of Iran, ixodid and argasid ticks were collected for arbovirus research. Five serotypes of arboviruses were obtained: Quaranfil, Thogoto, Wad Medani, Wanowrie and Crimean Haemorrhagic Fever-Congo. The isolation of all these arboviruses is reported for the first time in Iran.

Animals↗

[Tick-transmitted arbovirus in Maghreb].

The problem of arbovirus infections in Maghreb has been relatively neglected in the pst in spite of a rich diversity of biotopes, the presence of potential reservoirs and vectors, and their position on the flight path of the Palearctic-african bird migration systems, western branch. Moreover, West Nile virus has been isolated from southern Algeria since 1968. From 1979 to 1989, ticks were collected from wild birds, pigeons, bats, rodents, poultry, camels, wild boars, domestic mammals and man, and assayed for viruses. On the whole, 424 ticks were virologically studied from Morocco, 582 from Algeria and 601 from Tunisia. Four tick-borne arboviruses have been isolated so far: three from Morocco, Soldado (Nairovirus), Essaouria (Orbivirus) and Kala Iris (Orbivirus) from Ornithodoros (A.) maritimus ticks parasitizing marine birds, and one from Tunisia, Tunis (Phlebovirus), from Argas reflexus hermanni infesting domestic pigeons. Soldado virus may infect man working into colonies of gulls for ornithological or entomological purposes and this infection is associated with a self-limited febrile illness and pruritus. In addition, antibody to Essaouira virus was detected in a wild rodent in Morocco. On the contrary it is unlike that Tunis virus may infect man because A. r. hermanni is a strickly ornithophilic tick. However, Uukuniemi group antibody has been previously evidenced in wild rodents in Tunisia. Finally, it is not excluded that other, more pathogenic, arboviruses such as Congo-Crimean haemorrhagic fever might be accidentally introduced in this sensitive geographical area.

Africa, Northern↗

[Arbovirus infections. From virus, mosquitoes, animals and humans].

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.

Animals↗