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mosquito-borne - Top 30 Publications

Challenges of Vaccine Development for Zika Virus.

The emergence of outbreaks of Zika virus (ZIKV) in Brazil in 2015 was associated with devastating effects on fetal development and prompted a world health emergency and multiple efforts to generate an effective vaccine against infection. There are now more than 40 vaccine candidates in preclinical development and six in clinical trials. Despite similarities with other flaviviruses to which successful vaccines have been developed, such as yellow fever virus and Japanese Encephalitis virus, there are unique challenges to the development and clinical trials of a vaccine for ZIKV.

Antibiotic utilization and the role of suspected and diagnosed mosquito borne illness among adults and children with acute febrile illness in Pune, India.

Antibiotic resistance mechanisms originating in low- and middle- income countries are among the most common worldwide. Reducing unnecessary antibiotic use in India, the world's largest antibiotic consumer is crucial to control antimicrobial resistance globally. Limited data describing factors influencing Indian clinicians to start or stop antibiotics is available.

Global Transcriptome Analysis of Aedes aegypti Mosquitoes in Response to Zika Virus Infection.

Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti, which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.

Mountains, Melting Pot, and Microcosm: Health Care Delay and Dengue/Zika Interplay on Hawaii Island.

Human history in the Hawaiian Islands offers a sobering study in the population dynamics of infectious disease. The indigenous population numbering an estimated half million people prior to Western contact in 1778 was reduced to less than 24,000 by 1920. Much of the decline occurred in the earliest decades after contact with Western diseases including measles, chicken pox, polio, tuberculosis, and venereal disease. A recent outbreak on the Island of Hawaii (also called the Big Island) of imported dengue fever, an illness endemic in 100 countries affecting an estimated 100-400 million people worldwide, provides insights into the problems and prospects for health care policy in managing mosquito-borne disease in a multicultural setting of geographic isolation and health care provider shortage. This incident represents in microcosm a practice run, applicable in many contexts, for an initial localized appearance of Zika virus infection, with important lessons for effective health care management in a rapidly moving and fluid arena.

Mapping the spatial distribution of Aedes aegypti and Aedes albopictus.

Mosquito-borne infectious diseases, such as Rift Valley fever, Dengue, Chikungunya and Zika, have caused mass human death with the transnational expansion fueled by economic globalization. Simulating the distribution of the disease vectors is of great importance in formulating public health planning and disease control strategies. In the present study, we simulated the global distribution of Aedes aegypti and Aedes albopictus at a 5×5km spatial resolution with high-dimensional multidisciplinary datasets and machine learning methods Three relatively popular and robust machine learning models, including support vector machine (SVM), gradient boosting machine (GBM) and random forest (RF), were used. During the fine-tuning process based on training datasets of A. aegypti and A. albopictus, RF models achieved the highest performance with an area under the curve (AUC) of 0.973 and 0.974, respectively, followed by GBM (AUC of 0.971 and 0.972, respectively) and SVM (AUC of 0.963 and 0.964, respectively) models. The simulation difference between RF and GBM models was not statistically significant (p>0.05) based on the validation datasets, whereas statistically significant differences (p<0.05) were observed for RF and GBM simulations compared with SVM simulations. From the simulated maps derived from RF models, we observed that the distribution of A. albopictus was wider than that of A. aegypti along a latitudinal gradient. The discriminatory power of each factor in simulating the global distribution of the two species was also analyzed. Our results provided fundamental information for further study on disease transmission simulation and risk assessment.

Novel insect-specific Eilat virus-based chimeric vaccine candidates provide durable, mono- and multi-valent, single dose protection against lethal alphavirus challenge.

Most alphaviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates including birds, rodents, equids, humans and nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat virus (EILV), was described with an inability to infect vertebrate cells based on defective attachment and/or entry as well as a lack of genomic RNA replication. We investigated the utilization of EILV recombinant technology as a vaccine platform against eastern (EEEV) and Venezuelan equine encephalitis viruses (VEEV), two important pathogens of humans and domesticated animals. EILV chimeras containing structural proteins of EEEV or VEEV were engineered and successfully rescued in Aedes albopictus cells. Cryo-EM reconstructions at 8 and 11 Å of EILV/VEEV and EILV/EEEV, respectively, showed virion and glycoprotein spike structures similar to VEEV-Tc83 and other alphaviruses. The chimeras were unable to replicate in vertebrate cell lines or in brains of newborn mice when injected intracranially. Histopathologic examinations of the brain tissues showed no evidence of pathologic lesions, and were indistinguishable from those of mock-infected animals. A single-dose immunization of either monovalent or multivalent EILV chimera(s) generated neutralizing antibody responses and protected animals against lethal challenge 70 days later. Lastly, a single dose of monovalent EILV chimeras generated protective responses as early as day 1 post-vaccination, and partial or complete protection by day 6. These data demonstrate the safety, immunogenicity, and efficacy of novel insect-specific EILV-based chimeras as potential EEEV and VEEV vaccines.IMPORTANCE Mostly in the last decade, insect-specific viruses have been discovered in several arbovirus families. However, most of these viruses are not well studied and largely have been ignored. We explored use of the mosquito-specific alphavirus, Eilat virus (EILV), as an alphavirus vaccine platform in well-established disease models for eastern (EEE) and Venezuelan equine encephalitis (VEE). EILV-based chimeras replicated to high titers in a mosquito cell line, yet retained their host range restriction in vertebrates both in vitro and in vivo In addition, the chimeras generated immune responses that were higher than other human and/or equine vaccines. These findings indicate the feasibility of producing a safe, efficacious, mono- or multi-valent vaccine against the encephalitic alphaviruses, VEEV and EEEV. Lastly, these data demonstrate how host restricted, insect-specific viruses can be engineered to develop vaccines against related pathogenic arboviruses that cause severe disease in humans and domesticated animals.

The synergistic effect of nsP2-L618, nsP3-R117, and E2-K187 on the large plaque phenotype of chikungunya virus.

Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is the etiological agent of chikungunya fever. CHIKV re-emerged from 2004 onwards, and subsequently caused major outbreaks in many parts of the world including the Indian Ocean islands, Asia, and the Americas. In this study, a large plaque variant of CHIKV isolated from patient in Thailand was subjected to repeated cycles of plaque-purification in Vero cells. The resulting virus produced homogenous large plaques and showed a more pathogenic phenotype than the parental wild-type CHIKV. Whole genome analysis of the large plaque virus in comparison to parental isolate revealed a number of mutations, leading to the following amino acid changes: nsP2 (P618→L), nsP3 (G117→R), and E2 (N187→K). Eight recombinant CHIKVs were constructed to determine which amino acids mediated the large plaque phenotype. The results showed the recombinant virus which contains all three mutations, rCHK-L, produced significantly larger plaques than the other recombinant viruses (p < 0.01). Moreover, the plaque size of the other recombinant virus tended to be smaller if they contained only one or two of the large plaque associated mutations in the viral genome. In conclusion, the combination of all three residues (nsP2-L618, nsP3-R117, and E2-K187) is required to produce the large plaque phenotype of CHIKV.

Zika virus infection in travelers returning from countries with local transmission, Guangdong, China, 2016.

Zika virus (ZIKV) is a mosquito-borne virus spreading rapidly in the Americas, Africa, and Asia. No indigenous ZIKV infection had been seen in China. We monitored ZIKV infection among travelers returning to Enping county from ZIKV transmitting countries from 1 March to 10 April 2016.

Experimental Zika Virus Infection of Neotropical Primates.

The establishment of a sylvatic reservoir of Zika virus (ZIKV) in the Americas is dependent on the susceptibility of primates of sufficient population density, the duration and magnitude of viremia, and their exposure to the human mosquito-borne transmission cycle. To assess the susceptibility of squirrel (Saimiri sp.) and owl monkeys (Aotus sp.) to infection, we inoculated four animals of each species with ZIKV from the current epidemic. Viremia in the absence of detectible disease was observed in both species and seroconversion occurred by day 28. ZIKV was detected in the spleen of three owl monkeys: one at 7 days postinoculation (dpi) and two at 14 dpi. This study confirms the susceptibility to ZIKV infection of two Neotropical primate species that live in close proximity to humans in South America, suggesting that they could support a widespread sylvatic ZIKV cycle there. Collectively, establishment of a ZIKV sylvatic transmission cycle in South America would imperil eradication efforts and could provide a mechanism for continued exposure of humans to ZIKV infection and disease.

Chikungunya Virus Disease among Travelers-United States, 2014-2016.

Chikungunya virus is a mosquito-borne alphavirus that causes an acute febrile illness with severe polyarthralgia. The first local transmission of chikungunya virus in the Western Hemisphere was reported in December 2013. In the following year, the virus spread throughout much of the Americas and the number of cases among travelers increased substantially. We reviewed the epidemiology of chikungunya virus disease cases reported among U.S. travelers from 2014 to 2016. A total of 3,941 travel-acquired cases were reported from 49 states and the District of Columbia; 3,616 (92%) reported travel to other countries or territories in the Americas; the remaining 8% reported travel to Asia, Africa, or the Western Pacific. The most commonly reported travel destinations were the Dominican Republic, Puerto Rico, and Haiti. The largest number of cases (N = 2,780, 71%) had illness onset in 2014, followed by 2015 (N = 913, 23%) and 2016 (N = 248, 6%). Cases occurred in every month, but 70% of case-patients had illness onset from April to September, the months when mosquitoes are most likely to be active in the continental United States. Travel-acquired chikungunya cases will likely continue to occur and present a risk of introduction of the virus to locations in the continental United States. Clinicians and public health officials should be educated about the recognition, diagnosis, management, and timely reporting of chikungunya cases.

Recent advances in the development of antiviral therapeutics for Rift Valley fever virus infection.

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus endemic to sub-Saharan Africa and the Arabian Peninsula and the etiological agent of Rift Valley fever. Rift Valley fever is a disease of major public health and economic concern, affecting livestock and humans. In ruminants, RVFV infection is characterized by high mortality rates in newborns and near 100% abortion rates in pregnant animals. Infection in humans is typically manifested as a self-limiting febrile illness, but can lead to severe and fatal hepatitis, encephalitis, hemorrhagic fever or retinitis with partial or complete blindness. Currently, there are no specific treatment options available for RVFV infection. This review presents a summary of the therapeutic approaches that have been explored on the treatment of RVFV infection.

Zika clinical updates: implications for pediatrics.

Zika virus (ZIKV), a mosquito-borne flavivirus, has gained recognition over the past few years as an important new cause of congenital infection. As a result, it is critical that pediatricians understand its epidemiology, clinical presentation, clinical sequelae, and management.

Zika virus as a sexually transmitted pathogen.

Zika virus has recently emerged from an obscure mosquito-borne pathogen to an international public health concern. It is the first viral agent newly demonstrated to cause birth defects in several decades, and it is the only arbovirus now known to be transmitted sexually. The purpose of this review is to provide an overview of current understanding of sexual transmission of Zika virus and its possible clinical and public health consequences.

Vertical transmission of positive-sense single-stranded RNA viruses in plants as a model for arboviral induced teratogenesis.

Teratogenic viruses have increased public health importance with the emergence of Zika virus and a recent decline in rubella virus vaccination. Of the seven viruses known to cause birth defects in humans, three are mosquito-borne pathogens. Ethical oversight, compliance, rising costs, and the need for specialized training slow the pace of study of these human pathogens compared to study of similar teratogenic viruses in plants. Plant viruses have served as models for human viruses which can be applied to animal systems. This review describes the similar features of plant and animal teratogenic arboviruses and the common systems and barriers that are encountered during vertical transmission in the host.

Definitive tests for dengue fever: when and which should I use?

Dengue is a mosquito-borne viral disease that has established itself globally in both endemic and epidemic transmission cycles. While diagnostic decision-making for dengue is often guided by clinical judgement, definitive laboratory tests, including rapid point-of-care tests, have many advantages in the primary care setting. These include providing epidemiological data and diagnostic clarity for atypical cases, as well as contributing to patient education and compliance. This article discussed the types of diagnostic methods for dengue, when to use them and the appropriateness of each test. Viral detection diagnostic methods such as NS1 antigen assays are generally used within the first week of illness onset, whereas dengue serology testing is most appropriate after that time frame. Locally available rapid point-of-care tests, which include both assays in one convenient test kit, can enhance dengue diagnosis in an endemic setting.

Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages in culture cells.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa which affects both ruminants and humans. RVF causes serious damage to the livestock industry and is also a threat to public health. The Rift Valley fever virus has a segmented negative-stranded RNA genome consisting of Large (L)-, Medium (M)-, and Small (S)-segments. The live-attenuated MP-12 vaccine is immunogenic in livestock and humans, and is conditionally licensed for veterinary use in the U.S. The MP-12 strain encodes 23 mutations (nine amino acid substitutions) and is attenuated through a combination of mutations in the L-, M-, and S-segments. Among them, the M-U795C, M-A3564G, and L-G3104A mutations contribute to viral attenuation through the L- and M-segments. The M-U795C, M-A3564G, L-U533C, and L-G3750A mutations are also independently responsible for temperature-sensitive (ts) phenotype. We hypothesized that a serial passage of the MP-12 vaccine in culture cells causes reversions of the MP-12 genome. The MP-12 vaccine and recombinant rMP12-ΔNSs16/198 were serially passaged 25 times. Droplet digital PCR analysis revealed that the reversion occurred at L-G3750A during passages of MP-12 in Vero or MRC-5 cells. The reversion also occurred at M-A3564G and L-U533C of rMP12-ΔNSs16/198 in Vero cells. Reversion mutations were not found in MP-12 or the variant, rMP12-TOSNSs, in the brains of mice with encephalitis. This study characterized genetic stability of the MP-12 vaccine and the potential risk of reversion mutation at the L-G3750A ts mutation after excessive viral passages in culture cells.

The importance of human population characteristics in modeling Aedes aegypti distributions and assessing risk of mosquito-borne infectious diseases.

The mosquito Aedes aegypti has long been a vector for human illness in the Southeastern United States. In the past, it has been responsible for outbreaks of dengue, chikungunya, and yellow fever and, very recently, the Zika virus that has been introduced to the region. Multiple studies have modeled the geographic distribution of Ae. aegypti as a function of climate factors; however, this ignores the importance of humans to the anthropophilic biter. Furthermore, Ae. aegypti thrives in areas where humans have created standing water sites, such as water storage containers and trash. As models are developed to examine the potential impact of climate change, it becomes increasingly important to include the most comprehensive set of predictors possible.

Quantifying seasonal and diel variation in Anopheline and Culex human biting rates in Southern Ecuador.

Quantifying mosquito biting rates for specific locations enables estimation of mosquito-borne disease risk, and can inform intervention efforts. Measuring biting itself is fraught with ethical concerns, so the landing rate of mosquitoes on humans is often used as a proxy measure. Southern coastal Ecuador was historically endemic for malaria (Plasmodium falciparum and Plasmodium vivax), although successful control efforts in the 2000s eliminated autochthonous transmission (since 2011). This study presents an analysis of data collected during the elimination period.

Essential oils and their components as an alternative in the control of mosquito vectors of disease.

More than half of the human population is exposed to mosquito-borne infections. Climate change and the emergence of strains resistant to traditionally used insecticides have motivated the search of new agents for mosquito population control. Essential oils have been effective repellents and larvicidal agents.The aim of this work was to review research studies conducted in recent years on the larvicidal activity of essential oils and their components against Aedes, Anopheles and Culex mosquitoes, as well as the latest reports about their possible mechanism of action.

Biotechnological Applications of an Insect-Specific Alphavirus.

The coupling of viral and arthropod host diversity, with evolving methods of virus discovery, has resulted in the identification and classification of a growing number of novel insect-specific viruses (ISVs) that appear to be evolutionarily related to many human pathogens but have either lost or have yet to gain the ability to replicate in vertebrates. The discovery of ISVs has raised many questions as to the origin and evolution of many human pathogenic viruses and points to the role that arthropods may play in this evolutionary process. Furthermore, the use of ISVs to control the transmission of arthropod-borne viruses has been proposed and demonstrated experimentally. Previously, our laboratory reported on the discovery and characterization of Eilat virus (EILV), an insect-specific alphavirus that phylogenetically groups within the mosquito-borne clade of medically relevant alphaviruses, including eastern equine encephalitis virus (EEEV) and Venezuelan equine encephalitis virus (VEEV), as well as chikungunya virus (CHIKV). Despite its evolutionary relationship to these human pathogens, EILV is unable to replicate in vertebrate cells due to blocks at attachment/entry and RNA replication. We recently demonstrated that, using a chimeric virus approach, EILV could be utilized as a platform for vaccine and diagnostic development, serving as a proof-of-concept for other ISVs. Due to the vast abundance of ISVs, there is an untapped resource for the development of vaccines and diagnostics for a variety of human pathogens and further work in this area is warranted.

Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice.

Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly 1 and Guillain-Barré syndrome 2,3 as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis 4 , meningoencephalitis 5 and fatal encephalitis 6 . Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1 -/- ) mice, an infection model that exhibits high viral burden within the central nervous system. We show that systemic spread of ZIKV from the site of infection to the brain requires Ifnar1 deficiency in the haematopoietic compartment. However, spread of ZIKV within the central nervous system is supported by Ifnar1-deficient non-haematopoietic cells. Within this context, ZIKV infection of astrocytes results in breakdown of the blood-brain barrier and a large influx of CD8+ effector T cells. We also find that antiviral activity of CD8+ T cells within the brain markedly limits ZIKV infection of neurons, but, as a consequence, instigates ZIKV-associated paralysis. Taken together, our study uncovers mechanisms underlying ZIKV neuropathogenesis within a susceptible mouse model and suggests blood-brain barrier breakdown and T-cell-mediated neuropathology as potential underpinnings of ZIKV-associated neurological complications in humans.

Evaluation of the autochthonous transmission risk of Zika virus and other emerging mosquito-borne viral diseases in Catalonia (Spain).

The recent Zika virus epidemic has highlighted the potential risk of introducing the arbovirosis to Europe, especially within the Mediterranean region where the vector, Aedes albopictus, has become established as an invasive species. In this context, a comprehensive evaluation of the risk of introducing the Zika virus and other mosquito-borne viruses of public health importance in Catalonia (Spain) was carried out. This article summarises the results of the preliminary assessment and the recommendations for the public health preparedness and response plan against the threat posed by these emerging diseases.

A study of the chikungunya virus in humans in Turkey

Background/aim: The chikungunya virus (CHIKV) is a mosquito-borne disease and has recently been causing explosive outbreaks. The CHIKV has spread throughout all continents. Although the first chikungunya case imported from India to Turkey was reported in 2012, there is no detailed epidemiologic study in Turkey yet. The aim of this study was to investigate the seroprevalence of the CHIKV in Turkey. Materials and methods: ELISA was used to screen 500 random serum samples of healthy people collected from Kırıkkale, which is located in central Anatolia in Turkey. The results were verified by indirect immunofluorescence test (IIFT). Results: The results showed that 0.4% samples were positive for CHIKV. In the verification study with IIFT, CHIKV IgG type antibodies were defined as negative. To the best of our knowledge, this is the first serological study on the CHIKV in Turkey. Conclusion: Further studies are needed to elucidate the epidemiological situation in patients that have fever and arthritis.

Molecular characterization of novel mosquito-borne Rickettsia spp. from mosquitoes collected at the Demilitarized Zone of the Republic of Korea.

Rickettsiae are associated with a diverse range of invertebrate hosts. Of these, mosquitoes could emerge as one of the most important vectors because of their ability to transmit significant numbers of pathogens and parasites throughout the world. Recent studies have implicated Anopheles gambiae as a potential vector of Rickettsia felis. Herein we report that a metagenome sequencing study identified rickettsial sequence reads in culicine mosquitoes from the Republic of Korea. The detected rickettsiae were characterized by a genus-specific quantitative real-time PCR assay and sequencing of rrs, gltA, 17kDa, ompB, and sca4 genes. Three novel rickettsial genotypes were detected (Rickettsia sp. A12.2646, Rickettsia sp. A12.2638 and Rickettsia sp. A12.3271), from Mansonia uniformis, Culex pipiens, and Aedes esoensis, respectively. The results underscore the need to determine the Rickettsia species diversity associated with mosquitoes, their evolution, distribution and pathogenic potential.

Chikungunya Infection in Solid Organ Transplant Recipients.

Chikungunya virus (CHIKV) is an emerging mosquito-borne disease that causes acute febrile polyarthralgia and arthritis. CHIKV has spread rapidly to the Americas and, in Brazil, autochthonous cases are increasingly been reported. Solid organ transplant (SOT) recipients who travel to or live in CHIKV endemic areas are under high risk of acquiring the disease. Few data exist regarding the clinical characteristics of CHIKV infections in this population. We report the first case series of CHIKV infection in SOT recipients.

Host target-based approaches against arboviral diseases.

In the 20th century, socioeconomic and environmental changes facilitated the reintroduction of mosquitoes in developing cities, resulting in the reintroduction of mosquito-borne viral diseases and the dispersal of their causative agents in a worldwide scale. Recurrent outbreaks of arboviral diseases are being reported, even in regions without a previous history of arboviral disease transmission. Of note, arboviral infections represented approximately 30% of all emerging vector-borne diseases of the last decade. Therapeutic strategies against infectious viral diseases include the use of different classes of molecules that act directly on the pathogen and/or act by optimizing the host immune response. Drugs targeting the virus usually provide amelioration of symptoms by suppressing and controlling the infection. However, it is limited by the short-window of effectiveness, ineffectiveness against latent viruses, development of drug-resistant mutants and toxic side effects. Once disease may also be a consequence of an excessive, uncontrolled or misplaced inflammatory response, treatments that interfere in host immune response are interesting options and can be used isolated or in combination with virus-targeted therapies. The use of host-targeted therapies requires specific knowledge regarding host immune patterns that may trigger Dengue virus (DENV), Chikungunya virus (CHIKV) or Zika virus (ZIKV) disease.

Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents.

Acyl hydrazones are an important class of heterocyclic compounds promising pharmacological characteristics. Malaria is a life-threatening mosquito-borne blood disease caused by a plasmodium parasite. In some places, malaria can be treated and controlled with early diagnosis. However, some countries lack the resources to do this effectively.

Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene. However, CHIKV strains that encode an arginine codon in place of the opal stop codon have been described, and deep-sequencing analysis of a CHIKV isolate from the Caribbean identified both arginine and opal variants within this strain. Therefore, we hypothesized that the introduction of the arginine mutation in place of the opal termination codon may influence CHIKV virulence. We tested this by introducing the arginine mutation into a well-characterized infectious clone of a CHIKV strain from Sri Lanka and designated this virus Opal524R. This mutation did not impair viral replication kinetics in vitro or in vivo Despite this, the Opal524R virus induced significantly less swelling, inflammation, and damage within the feet and ankles of infected mice. Further, we observed delayed induction of proinflammatory cytokines and chemokines, as well as reduced CD4+ T cell and NK cell recruitment compared to those in the parental strain. Therefore, the opal termination codon plays an important role in CHIKV pathogenesis, independently of effects on viral replication.IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes significant outbreaks of viral arthralgia. Studies with CHIKV and other alphaviruses demonstrated that the opal termination codon within nsP3 is highly conserved. However, some strains of CHIKV and other alphaviruses contain mutations in the opal termination codon. These mutations alter the virulence of related alphaviruses in mammalian and mosquito hosts. Here, we report that a clinical isolate of a CHIKV strain from the recent outbreak in the Caribbean islands contains a mixture of viruses encoding either the opal termination codon or an arginine mutation. Mutating the opal stop codon to an arginine residue attenuates CHIKV-induced disease in a mouse model. Compared to infection with the opal-containing parental virus, infection with the arginine mutant causes limited swelling and inflammation, as well as dampened recruitment of immune mediators of pathology, including CD4+ T cells and NK cells. We propose that the opal termination codon plays an essential role in the induction of severe CHIKV disease.

Zika virus: what we need to know?

Zika virus is one of the emerging viruses and is of significant threat to human health globally. It is a mosquito borne flavivirus similar to dengue, yellow fever, and West Nile viruses. It was reported about 5 decades ago and then it spreads to different parts of the world. Large outbreaks were reported on Yap Islands in 2007. Now it has gained wide attention globally by health communities. Major vector for virus transmission is Aedes aegypti mosquito. ZIKV infection is mostly asymptomatic but it is also responsible to cause mild influenza like illness to serious manifestations. There is no specific anti-viral treatment is available for ZIKV infection. The virus disseminates very fast due to which it possesses a serious threat especially in those areas where there is lack of specific immunity against virus. Little knowledge is available on its transmission and pathogenicity. Although virus was discovered years ago but its genomic structure is not clearly understood yet. In this review we focus on the current knowledge of epidemiology of ZIKV, its transmission, its structural biology, different aspects of diagnosis and diagnostic challenges as well as highlighted appropriates antiviral drugs and vaccines regarding treatment.

Lipids and Pathogen Blocking by Wolbachia.

Mosquito-borne viruses are major human pathogens. Introducing Wolbachia into mosquitoes could reduce disease burdens because these bacteria block virus transmission. How Wolbachia does this is unclear, but new data show that modulation of host-cell lipids is critical.