The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry.

Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced cell binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.

Interactions between capsid and viral RNA regulate Chikungunya virus translation in a host-specific manner.

Alphaviruses are positive sense, RNA viruses commonly transmitted by an arthropod vector to a mammalian or avian host. In recent years, a number of the Alphavirus members have reemerged as public health concerns. Transmission from mosquito vector to vertebrate hosts requires an understanding of the interaction between the virus and both vertebrate and insect hosts to develop rational intervention strategies. The current study uncovers a novel role for capsid protein during Chikungunya virus replication whereby the interaction with viral RNA in the E1 coding region regulates protein synthesis processes early in infection. Studies done in both the mammalian and mosquito cells indicate that interactions between viral RNA and capsid protein have functional consequences that are host species specific. Our data support a vertebrate-specific role for capsid:vRNA interaction in temporally regulating viral translation in a manner dependent on the PI3K-AKT-mTOR pathway.

Identification of Peptide Binders to Truncated Recombinant Chikungunya Virus Envelope Protein 2 Using Phage Display Technology and Their In Silico Characterization.

AIM: To identify and characterize peptide binders to truncated recombinant chikungunya virus envelope protein 2. BACKGROUND: Despite extensive research on the chikungunya virus (CHIKV), the specific antiviral treatment's unavailability has stressed the need for the urgent development of therapeutics. The Envelope protein 2 (E2) of CHIKV that displays putative receptor binding sites and specific epitopes for virus neutralizing antibodies is a critical target for the therapeutic intervention. OBJECTIVE: The study aims to identify the unique peptides that can bind to truncated E2 protein of CHIKV and further explore their properties as potential therapeutic candidate. METHODS: A stretch of CHIKV-E2 (rE2), which is prominently exposed on the surface of virion, was used as bait protein to identify peptide binders to the CHIKV-rE2 using a 12-mer phage display peptide library. Three rounds of biopanning yielded several peptide binders to CHIKV-rE2 and their binding affinities were compared by phage ELISA. Additionally, a fully flexible-blind docking simulation investigated the possible binding modes of the selected peptides. Furthermore, the selected peptides were characterized and their ADMET properties were explored in silico. RESULTS: Five peptides were identified as potential binders based on their robust reactivity to the bait protein. The selected peptides appeared to interact with the crucial residues that were notably exposed on the surface of E1-E2 trimeric structure. The explored in silico studies suggested their non-allergenicity, non-toxicity and likeliness to be antiviral. CONCLUSION: The potential binding peptides of CHIKV-rE2 protein were identified using phage display technology and characterized in silico. The selected peptides could be further used for the development of therapeutics against the CHIKV infection.>.

Natural antiviral compound silvestrol modulates human monocyte-derived macrophages and dendritic cells.

Outbreaks of infections with viruses like Sars-CoV-2, Ebola virus and Zika virus lead to major global health and economic problems because of limited treatment options. Therefore, new antiviral drug candidates are urgently needed. The promising new antiviral drug candidate silvestrol effectively inhibited replication of Corona-, Ebola-, Zika-, Picorna-, Hepatis E and Chikungunya viruses. Besides a direct impact on pathogens, modulation of the host immune system provides an additional facet to antiviral drug development because suitable immune modulation can boost innate defence mechanisms against the pathogens. In the present study, silvestrol down-regulated several pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, CCL2, CCL18) and increased TNF-α during differentiation and activation of M1-macrophages, suggesting that the effects of silvestrol might cancel each other out. However, silvestrol amplified the anti-inflammatory potential of M2-macrophages by increasing expression of anti-inflammatory surface markers CD206, TREM2 and reducing release of pro-inflammatory IL-8 and CCL2. The differentiation of dendritic cells in the presence of silvestrol is characterized by down-regulation of several surface markers and cytokines indicating that differentiation is impaired by silvestrol. In conclusion, silvestrol influences the inflammatory status of immune cells depending on the cell type and activation status.

Synthesis of 4'-Substituted-2'-Deoxy-2'-α-Fluoro Nucleoside Analogs as Potential Antiviral Agents.

Nucleoside analogs are widely used for the treatment of viral diseases (Hepatitis B/C, herpes and human immunodeficiency virus, HIV) and various malignancies. ALS-8176, a prodrug of the 4'-chloromethyl-2'-deoxy-2'-fluoro nucleoside ALS-8112, was evaluated in hospitalized infants for the treatment of respiratory syncytial virus (RSV), but was abandoned for unclear reasons. Based on the structure of ALS-8112, a series of novel 4'-modified-2'-deoxy-2'-fluoro nucleosides were synthesized. Newly prepared compounds were evaluated against RSV, but also against a panel of RNA viruses, including Dengue, West Nile, Chikungunya, and Zika viruses. Unfortunately, none of the compounds showed marked antiviral activity against these viruses.

An amino acid change in nsP4 of chikungunya virus confers fitness advantage in human cell lines rather than in Aedes albopictus.

Chikungunya virus (CHIKV) has caused large-scale epidemics of fever, rash and arthritis since 2004. This unprecedented re-emergence has been associated with mutations in genes encoding structural envelope proteins, providing increased fitness in the secondary vector Aedes albopictus. In the 2008-2013 CHIKV outbreaks across Southeast Asia, an R82S mutation in non-structural protein 4 (nsP4) emerged early in Malaysia or Singapore and quickly became predominant. To determine whether this nsP4-R82S mutation provides a selective advantage in host cells, which may have contributed to the epidemic, the fitness of infectious clone-derived CHIKV with wild-type nsP4-82R and mutant nsP4-82S were compared in Ae. albopictus and human cell lines. Viral infectivity, dissemination and transmission in Ae. albopictus were not affected by the mutation when the two variants were tested separately. In competition, the nsP4-82R variant showed an advantage over nsP4-82S in dissemination to the salivary glands, but only in late infection (10 days). In human rhabdomyosarcoma (RD) and embryonic kidney (HEK-293T) cell lines coinfected at a 1 : 1 ratio, wild-type nsP4-82R virus was rapidly outcompeted by nsP4-82S virus as early as one passage (3 days). In conclusion, the nsP4-R82S mutation provides a greater selective advantage in human cells than in Ae. albopictus, which may explain its apparent natural selection during CHIKV spread in Southeast Asia. This is an unusual example of a naturally occurring mutation in a non-structural protein, which may have facilitated epidemic transmission of CHIKV.

Differential susceptibility & replication potential of Vero E6, BHK-21, RD, A-549, C6/36 cells & Aedes aegypti mosquitoes to three strains of chikungunya virus.

Background & objectives: Chikungunya virus (CHIKV), a mosquito-borne arthritogenic virus causes infections ranging from febrile illness to debilitating polyarthralgia in humans. Re-emergence of the virus has affected millions of people in Africa and Asia since 2004. During the outbreak, a new lineage of the virus has evolved as an adaptation for enhanced replication and transmission by Aedes albopictus mosquito. A study was designed to compare the susceptibility of four vertebrate cell lines, namely Vero E6 (African green monkey kidney), BHK-21 (Baby hamster kidney), RD (human rhabdomyosarcoma), A-549 (human alveolar basal epithelial cell) and C6/36 (Ae. albopictus) to Asian genotype and two lineages of East, Central and South African (E1:A226 and E1:A226V) of CHIKV. Methods: One-step growth kinetics of different CHIKV strains was carried out in the above five cell lines to determine the growth kinetics and virus yield. Virus titre was determined by 50 per cent tissue culture infectious dose assay and titres were calculated by the Reed and Muench formula. Growth and virus yield of the three strains in Ae. aegypti mosquitoes was studied by intrathoracic inoculation and virus titration in Vero E6 cell line. Results: Virus titration showed Vero E6, C6/36 and BHK-21 cell lines are high virus yielding with all the three lineages while RD and A-549 yielded low virus titres. C6/36 cell line was the most sensitive and yielded the maximum titre. Ae. aegypti mosquitoes, when inoculated with high titre virus, yielded an almost equal growth with the three strains while rapid growth of E1:A226V and Asian strain was observed with 1 log virus. Interpretation & conclusions: C6/36 cell line was found to be the most sensitive and high yielding for CHIKV irrespective of lineages while Vero E6 and BHK-21 cell lines yielded high titres and may find application for vaccine/diagnostic development. Infection of Ae. aegypti mosquitoes with the three CHIKV strains gave almost identical pattern of growth.

Macropinocytosis dependent entry of Chikungunya virus into human muscle cells.

Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia with high morbidity. CHIKV is now considered endemic in many countries across Asia and Africa. In this study, the susceptibility of various human, mammalian and mosquito cell lines to CHIKV infection was evaluated. CHIKV infection was found to be cell-type dependent and virus strain-specific. Furthermore, SJCRH30 (human rhabdomyosarcoma cell line) was showed to be highly permissive to CHIKV infection, with maximum production of infectious virions observed at 12 h.p.i. Pre-infection treatment of SJCRH30 with various inhibitors of endocytosis, including monodansylcadaverine (receptor-mediated endocytic inhibitor), dynasore (clathrin-mediated endocytic inhibitor), as well as filipin (caveolin-mediated endocytosis inhibitor), resulted in minimal inhibition of CHIKV infection. In contrast, dose-dependent inhibition of CHIKV infection was observed with the treatment of macropinocytosis inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Furthermore, siRNA-mediated knockdown of sortin nexin 9 (SNX9) a protein involved in macropinosome formation, also resulted in a significant dose-dependent reduction in viral titre. By performing a virus entry assay, CHIKV particles were also observed to colocalize with FITC-dextran, a macropinosome marker. This study shows for the first time, that the infectious entry of CHIKV into human muscle cells is mediated by macropinocytosis. Together, the data from this study may pave the way for the development of specific inhibitors that target the entry process of CHIKV into cells.

Glycan-dependent chikungunya viral infection divulged by antiviral activity of NAG specific chi-like lectin.

Highly pathogenic alphaviruses display complex glycans on their surface. These glycans play a crucial role in viral pathogenesis by facilitating glycan-host interaction during viral entry which can be targeted. Various studies have reported antiviral activity of lectins that bind to the glycans present on the surface of enveloped viruses. This study evaluates the antiviral potential of a chitinase (chi)-like lectin from Tamarind (TCLL) having specificity for N-acetylglucosamine (NAG). Thus, TCLL might bind to N-glycan rich surface of alphavirus and inhibit the entry of virus into the host cells. The direct treatment of TCLL with virus reduced the virus infection. Remarkably, the addition of NAG to TCLL abolished antiviral activity confirming that NAG binding property of TCLL is accountable for its antiviral activity. Further, an ELISA assay confirmed the binding of TCLL to alphaviruses. Taken together, this study will prove to be beneficial in developing lectin therapeutics targeting alphavirus glycan.

Chikungunya-vesicular stomatitis chimeric virus targets and eliminates brain tumors.

Vesicular stomatitis virus (VSV) shows potential for targeting and killing cancer cells, but can be dangerous in the brain due to its neurotropic glycoprotein. Here we test a chimeric virus in which the VSV glycoprotein is replaced with the Chikungunya polyprotein E3-E2-6K-E1 (VSVΔG-CHIKV). Control mice with brain tumors survived a mean of 40 days after tumor implant. VSVΔG-CHIKV selectively infected and eliminated the tumor, and extended survival substantially in all tumor-bearing mice to over 100 days. VSVΔG-CHIKV also targeted intracranial primary patient derived melanoma xenografts. Virus injected into one melanoma spread to other melanomas within the same brain with little detectable infection of normal cells. Intravenous VSVΔG-CHIKV infected tumor cells but not normal tissue. In immunocompetent mice, VSVΔG-CHIKV selectively infected mouse melanoma cells within the brain. These data suggest VSVΔG-CHIKV can target and destroy brain tumors in multiple animal models without the neurotropism associated with the wild type VSV glycoprotein.

Caracterização clínica das síndromes neurológicas durante a tríplice epidemia de arboviroses em Salvador, Bahia, Brasil / Clinical characterization of neurological syndromes during the triple arbovirus epidemic in Salvador, Bahia, Brazil

INTRODUÇÃO: Os arbovírus são vírus transmitidos por vetores artrópodes e diversos deles podem ser encontrados em cocirculação no Brasil. Complicações neurológicas associadas aos vírus dengue (DENV), chikungunya (CHIKV) e zika (ZIKV) já foram descritas anteriormente na literatura. Durante a tríplice epidemia de arboviroses houve um aumento importante de casos neurológicos, principalmente síndrome de Guillain-Barré (GBS).MATERIAL E MÉTODOS: Iniciada uma vigilância hospitalar para síndromes neurológicas agudas, onde foram incluídos pacientes avaliados em unidades neurológicas de dois hospitais de referência em Salvador/BA durante o período de maio de 2015 a abril de 2016.RESULTADOS: Cinco artigos foram escritos para melhor caracterização do tema. Dois casos de GBS clássico associado ao ZIKV foram publicados durante o surto supracitado, sendo um dos primeiros artigos no Brasil relacionando as duas doenças. Foi realizada a descrição com detalhes o caso da rara síndrome opsoclonus-mioclonusencefalite (OMAS), no qual a pacientes e apresentara com alteração de sensório, movimentos oculares anárquicos e ataxia. Na investigação foram detectados o DENV e CHIKV no plasma e o CHIKV no líquor pelo RTPCR.A paciente foi tratada com corticoide venoso e teve alta com melhora funcional, semalterações cognitivas ou motoras. Uma série de 5 casos descreveu com mais detalhe uma forma neurológica mais leve, a polineuropatia sensitiva reversível (RSP). Todos os pacientes apresentaram quadros transitórios, exclusivamente de alterações sensitivas; dois casos tinham evidência de infecção recente por ZIKV e outros 2 por CHIKV. Uma série de casos de pacientes com GBS, avaliou 14 indivíduos, sendo que 50% destes apresentavam variantes dessa doença. Havia uma maior prevalência de acometimento do nervo facial do que nas populações previamente estudadas. Prevaleceu a forma desmielinizante na eletroneuromiografia desses pacientes. Setenta e dois por cento dos pacientes foram reavaliados em 30 dias e todos tiveram ótima recuperação funcional. Por fim foi escrito um estudo de corte transversal que descreveu as síndromes neurológicas ocorridas em Salvador durante o surto da tríplice arboviral com 29 pacientes acompanhados; aproximadamente 50% se apresentaram com GBS ou suas variantes. Outras manifestações como encefalites, mielites, OMAS e RSP foram descritas. Cerca de 80% dos pacientes apresentavam evidência sorológica de infecção recente por ZIKV ou CHIKV. CONCLUSÃO: Foram descritas manifestações neurológicas como GBS e outras síndromes relacionadas às arboviroses. O melhor conhecimento dessas manifestações pode trazer benefício para prevenção, diagnóstico e tratamento dessas doenças, assim como melhorar as ações em saúde pública para combate às complicações por arboviroses

INTODUCTION: Arboviruses are viruses transmitted by arthropod vectors and several ofthem can be found in cocirculation in Brazil. Neurological complications associated with dengue virus (DENV), chikungunya (CHIKV) and zika (ZIKV) have previously been described in the literature. During the triple epidemic of arboviruses there was a significant increase in neurological cases, mainly Guillain-Barré syndrome (GBS). MATERIAL AND METHODS: A hospital surveillance for acute neurological syndromes was started, which included patients evaluated in neurological units of two reference hospitals in Salvador / BA during the period from May 2015 to April 2016. RESULTS: Five articles were written to better characterize the clinical manifestations. Two cases of classic GBS associated with ZIKV were published during triple arbovirosis outbreak, being one of the first articles in Brazil correlating the two diseases. A detailed description was made of the rare opsoclonus-myoclonus encephalitis syndrome (OMAS), in another article, in which the patient presented with confusion, anarchical ocular movements and ataxia. DENV and CHIKV were detected in plasma and CHIKV in the CSF by RT-PCR. The patient was treated with venous corticosteroids and was discharged with functional improvement, without cognitive or motor alterations. A series of 5 cases described a milder neurological form, the reversible sensory polyneuropathy (RSP). All patients presented only with transient sensory disturbances; two cases evidenced recent infection by ZIKV and another 2 by CHIKV. A case-series of GBS patients evaluated 14 individuals, with 50% of them presenting with GBS subtypes. There was a higher prevalence of facial nerve involvement than in the previously studied populations. The demyelinating form prevailed in the electroneuromyography studies of these patients. Seventy-two percent of the patients were reassessed in 30 days and all had an optimal functional recovery. Finally, a cross-sectional study was written and described the neurological syndromes that occurred in Salvador during the outbreak of the triple arboviral with 29 patients followed up; approximately 50% presented with GBS or its subtypes. Other manifestations such as encephalitis, myelitis, OMAS and RSP were described. About 80% of the patients had serological evidence of recent infection by ZIKV or CHIKV. CONCLUSION: Neurological manifestations such as GBS and other syndromes related to arbovirus have been described. The better knowledge of these manifestations can benefit the prevention, diagnosis and treatment of these diseases, as well as to improve the actions in public health to combat complications by arbovirosis

Obatoclax Inhibits Alphavirus Membrane Fusion by Neutralizing the Acidic Environment of Endocytic Compartments.

As new pathogenic viruses continue to emerge, it is paramount to have intervention strategies that target a common denominator in these pathogens. The fusion of viral and cellular membranes during viral entry is one such process that is used by many pathogenic viruses, including chikungunya virus, West Nile virus, and influenza virus. Obatoclax, a small-molecule antagonist of the Bcl-2 family of proteins, was previously determined to have activity against influenza A virus and also Sindbis virus. Here, we report it to be active against alphaviruses, like chikungunya virus (50% effective concentration [EC50] = 0.03 µM) and Semliki Forest virus (SFV; EC50 = 0.11 µM). Obatoclax inhibited viral entry processes in an SFV temperature-sensitive mutant entry assay. A neutral red retention assay revealed that obatoclax induces the rapid neutralization of the acidic environment of endolysosomal vesicles and thereby most likely inhibits viral fusion. Characterization of escape mutants revealed that the L369I mutation in the SFV E1 fusion protein was sufficient to confer partial resistance against obatoclax. Other inhibitors that target the Bcl-2 family of antiapoptotic proteins inhibited neither viral entry nor endolysosomal acidification, suggesting that the antiviral mechanism of obatoclax does not depend on its anticancer targets. Obatoclax inhibited the growth of flaviviruses, like Zika virus, West Nile virus, and yellow fever virus, which require low pH for fusion, but not that of pH-independent picornaviruses, like coxsackievirus A9, echovirus 6, and echovirus 7. In conclusion, obatoclax is a novel inhibitor of endosomal acidification that prevents viral fusion and that could be pursued as a potential broad-spectrum antiviral candidate.

Design and Validation of Novel Chikungunya Virus Protease Inhibitors.

Chikungunya virus (CHIKV; genus Alphavirus) is the causative agent of chikungunya fever. CHIKV replication can be inhibited by some broad-spectrum antiviral compounds; in contrast, there is very little information about compounds specifically inhibiting the enzymatic activities of CHIKV replication proteins. These proteins are translated in the form of a nonstructural (ns) P1234 polyprotein precursor from the CHIKV positive-strand RNA genome. Active forms of replicase enzymes are generated using the autoproteolytic activity of nsP2. The available three-dimensional (3D) structure of nsP2 protease has made it a target for in silico drug design; however, there is thus far little evidence that the designed compounds indeed inhibit the protease activity of nsP2 and/or suppress CHIKV replication. In this study, a set of 12 compounds, predicted to interact with the active center of nsP2 protease, was designed using target-based modeling. The majority of these compounds were shown to inhibit the ability of nsP2 to process recombinant protein and synthetic peptide substrates. Furthermore, all compounds found to be active in these cell-free assays also suppressed CHIKV replication in cell culture, the 50% effective concentration (EC50) of the most potent inhibitor being ∼1.5 µM. Analysis of stereoisomers of one compound revealed that inhibition of both the nsP2 protease activity and CHIKV replication depended on the conformation of the inhibitor. Combining the data obtained from different assays also indicates that some of the analyzed compounds may suppress CHIKV replication using more than one mechanism.

La explosión del virus de sika / The explosion of zika virus / A explosão do vírus do zika

El siguiente informe aborda la historia de los primeros casos de Zika, su disperción y complicaciones. Aborda también los rasgos diferenciales entre zika, dengue y chikungunya. Luchacontra el vector y vacuna contra el dengue.

The following report deals with the story of the first cases of Zika, their dispersal and complications. also discusses the distinguishing features between zika, dengue and chikungunya. Fight vector and dengue vaccine.

O relatório a seguir lida com a história dos primeiros casos de Zika, sua dispersão e complicações. também discute as características distintivas entre Zika, dengue e chikungunya. lutavetor ea dengue vacina.

Antiviral activity of silymarin against chikungunya virus.

The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection.

Manifestaciones mucocutáneas de la fiebre chikungunya / Mucocutaneous manífestatíons of chíkungunya fever

La fiebre chikungunya (FC) es una enfermedad vírica trasmitida por Aedes aegypti y Aedes albopictus infectados. El virus chikungunya es un ARN virus perteneciente a la género Alphavirus de la familia Togaviridae. La FC manifiesta una tendencia epidémica secuelar, cíclica y estacional. El ciclo natural del virus es humano-mosquito-humano. Actualmente la trasmisión autóctona se ha registrado en 36 países/territorios de la región de las Américas, en República Dominicana (64,7 %), Guadalupe (10,5 %), Martinica (8,8 %) Y Haití (8,5 %) los que han reportado el mayor número de casos y defunciones por fiebre. En Perú, actualmente no se ha reportado transmisión autóctona de FC. El virus chikungunya causa una enfermedad febril en la mayoría de los pacientes, con un período de incubación de 2 a 4 días a partir de la mordida del mosquito. La viremia persiste por 5 días desde el inicio de los síntomas. Las manifestaciones más comunes son fiebre (92 %), artralgia (87 %), dorsalgia (67 %), y cefalea (62 %). Algunas de estas enfermedades consideradas como diagnóstico diferencial son la leptospirosis, el dengue, la malaria, la meningitis y la fiebre reumática. Las manifestaciones cutáneas ocurrieron en aproximadamente 77 % de los casos, la mayoría de ellos presenta un exantema generalizado que consiste en máculas o pápulas no coalescentes, hiperpigmentaclán, xerosis, úlceras genitales. Hay ciertas diferencias en la presentación de la FC en niños y adultos. Mientras que en niños los cambios pigmentarios son generalizados, en adultos se presenta la forma centrofacial o pigmentación melasma like. Existen reportes de empeoramiento de lesiones de psoriasis o dermatitis atópica requieren manejo específico por parte del dermatólogo.

Chikungunya fever is a viral disease transmitted by infected Aedes aegypti and A. albopictus. The virus name (CHIK) is an RNA virus belonging to the genus Alphavirus of the Togaviridae family. Chikungunya fever manifests seque lar, cyclical and seasonal epidemic trend. The natural cycle of the virus is human-mosquito-human. Currently the autochthonous transmission is registe red in 36 countries / territories in the region of the Americas; being Dominican Republic (64,7 %), Guadeloupe (10,5 %), Martinique (8,8 %) and Haiti (8,5 %) where were reported the highest number of cases and deaths from chikungunya fever. Autocluhonous transmission of chikungunya fever currently has not been reported in Peru. The CH1K fever virus causes disease in most patients, with an incubation period of 2-4 days after the bite of the mosquito. The viremia persists for 5 days from the onset of symptoms. The most common manifestations are fever (92 %), arthralgia (87 %), back pain (67 %), and headache (62 %). Some of these diseases are considered as a differential diagnosis: leptospirosis, dengue, malaria, meningitis, rheumatic fever. Cutaneous manifestations occur in approximately 77 % of cases, most of them presents a generalized rash consisting of macules or papules coalescing, hyperpigmentation, xerosis, genital ulcers. There are certain differences in the presentation of chikungunya fever in children and adults. While children are widespread pigmentary changes in the midface adult form or pigmentation like melasma occurs. There are reports of worsening psoriasis lesions or atopic dermatitis require specific handling by the dermatologist.

Chikungunya virus adaptation to a mosquito vector correlates with only few point mutations in the viral envelope glycoprotein.

Like most arthropod-borne viruses (arboviruses), chikungunya virus (CHIKV) is a RNA virus maintained in nature in an alternating cycle of replication between invertebrate and vertebrate hosts. It has been assumed that host alternation restricts arbovirus genome evolution and imposes fitness trade-offs. Despite their slower rates of evolution, arboviruses still have the capacity to produce variants capable to exploit new environments. To test whether the evolution of the newly emerged epidemic variant of CHIKV (E1-226V) is constrained by host alternation, the virus was alternately-passaged in hamster-derived BHK-21 cells and Aedes aegypti-derived Aag-2 cells. It was also serially-passaged in BHK-21 or Aag-2 cells to promote adaptation to one cell type and presumably, fitness cost in the bypassed cell type. After 30 passages, obtained CHIKV strains were genetically and phenotypically characterized using in vitro and in vivo systems. Serially- and alternately-passaged strains can be distinguished by amino-acid substitutions in the E2 glycoprotein, responsible for receptor binding. Two substitutions at positions E2-64 and E2-208 only lower the dissemination of the variant E1-226V in Ae. aegypti. These amino-acid changes in the E2 glycoprotein might affect viral infectivity by altering the interaction between CHIKV E1-226V and the cellular receptor on the midgut epithelial cells in Ae. aegypti but not in Aedesalbopictus.

Comparative evaluation of the diagnostic potential of recombinant envelope proteins and native cell culture purified viral antigens of Chikungunya virus.

Despite the fact that Chikungunya resurgence is associated with epidemic of unprecedented magnitude, there are challenges in the field of its clinical diagnosis. However, serological tests in an ELISA format provide a rapid tool for the diagnosis of Chikungunya infection. Indeed, ELISAs based on recombinant proteins hold a great promise as these methods are cost effective and are free from the risk of handling biohazardous material. In this study, the performance of recombinant CHIKV antigens was compared in various ELISA formats for the diagnosis of Chikungunya. Two recombinant antigens derived from the envelope proteins of Chikungunya virus were prepared and evaluated by comparing their competence for detecting circulating antibodies in serum samples of patients infected with CHIKV using MAC-ELISA and indirect IgM-ELISA. The efficacy of the recombinant antigens was also compared with the native antigen. The indirect antibody capture IgM microplate ELISA revealed ≥90% concordance with the native antigen in detecting the CHIKV specific IgM antibodies whereas the recombinant antigen based MAC-ELISA showed 100% specificity. The recombinant antigens used in this study were effective and reliable targets for the diagnosis of CHIKV infection and also provide an alternative for native antigen use which is potentially biohazardous.

[Foro de opinión] - Fiebre chikungunya / Fever chikungunya

La fiebre chikungunya (en idioma makonde: chikungunya,que significa hombre doblado o retorcido), conocida tambiéncomo artritis epidémica chikungunya. Es producida por unvirus ARN del género alfavirus, familia Togaviridae, el cuales transmitido por dos especies de mosquitos: Aedes aegyptiy Aedes albopictus.

Chikungunya (in Makonde Language: chikungunya,which means man bent or twisted), also knownas chikungunya epidemic arthritis. It is produced by aalphavirus RNA virus genus, family Togaviridae, whichIt is transmitted by two species of mosquito: Aedes aegyptiand Aedes albopictus.

Dissemination and transmission of the E1-226V variant of chikungunya virus in Aedes albopictus are controlled at the midgut barrier level.

Emergence of arboviruses could result from their ability to exploit new environments, for example a new host. This ability is facilitated by the high mutation rate occurring during viral genome replication. The last emergence of chikungunya in the Indian Ocean region corroborates this statement since a single viral mutation at the position 226 on the E1 glycoprotein (E1-A226V) was associated with enhanced transmission by the mosquito Aedes albopictus in regions where the major mosquito vector, Aedes aegypti, is absent.We used direct competition assays in vivo to dissect out the mechanisms underlying the selection of E1-226V by Ae. albopictus. When the original variant E1-226A and the newly emerged E1-226V were provided in the same blood-meal at equal titers to both species of mosquitoes, we found that the proportion of both variants was drastically different in the two mosquito species. Following ingestion of the infectious blood-meal, the E1-226V variant was preferentially selected in Ae. albopictus, whereas the E1-226A variant was sometimes favored in Ae. aegypti. Interestingly, when the two variants were introduced into the mosquitoes by intrathoracic inoculations, E1-226V was no longer favored for dissemination and transmission in Ae. albopictus, showing that the midgut barrier plays a key role in E1-226V selection.This study sheds light on the role of the midgut barrier in the selection of novel arbovirus emerging variants. We also bring new insight into how the pre-existing variant E1-226V was selected among other viral variants including E1-226A. Indeed the E1-226V variant present at low levels in natural viral populations could rapidly emerge after being selected in Ae. albopictus at the midgut barrier level.