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1.
CMAJ ; 195(31): E1030-E1037, 2023 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-37580072

RESUMEN

BACKGROUND: During the first year of the COVID-19 pandemic, the proportion of reported cases of COVID-19 among Canadians was under 6%. Although high vaccine coverage was achieved in Canada by fall 2021, the Omicron variant caused unprecedented numbers of infections, overwhelming testing capacity and making it difficult to quantify the trajectory of population immunity. METHODS: Using a time-series approach and data from more than 900 000 samples collected by 7 research studies collaborating with the COVID-19 Immunity Task Force (CITF), we estimated trends in SARS-CoV-2 seroprevalence owing to infection and vaccination for the Canadian population over 3 intervals: prevaccination (March to November 2020), vaccine roll-out (December 2020 to November 2021), and the arrival of the Omicron variant (December 2021 to March 2023). We also estimated seroprevalence by geographical region and age. RESULTS: By November 2021, 9.0% (95% credible interval [CrI] 7.3%-11%) of people in Canada had humoral immunity to SARS-CoV-2 from an infection. Seroprevalence increased rapidly after the arrival of the Omicron variant - by Mar. 15, 2023, 76% (95% CrI 74%-79%) of the population had detectable antibodies from infections. The rapid rise in infection-induced antibodies occurred across Canada and was most pronounced in younger age groups and in the Western provinces: Manitoba, Saskatchewan, Alberta and British Columbia. INTERPRETATION: Data up to March 2023 indicate that most people in Canada had acquired antibodies against SARS-CoV-2 through natural infection and vaccination. However, given variations in population seropositivity by age and geography, the potential for waning antibody levels, and new variants that may escape immunity, public health policy and clinical decisions should be tailored to local patterns of population immunity.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Pandemias , Estudios Seroepidemiológicos , Alberta , Anticuerpos Antivirales
2.
iScience ; 25(10): 105234, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36267915

RESUMEN

Activated-to-memory transitioning CD4+ T cells display elevated expression of the HIV-1 co-receptor CCR5 and are more prone to HIV-1 latent infection. Here, we show that p53-regulated miRNA-103 downmodulates CCR5 levels in CD4+ T lymphocytes. We reveal that miRNA-103 mimics, as well as Nutlin-3, an inhibitor of Mdm2-mediated p53 degradation, decrease CCR5-dependent HIV-1 infection. Using a dual-reporter virus, we subsequently validate that in transitioning CD4+ T cells, Nutlin-3 treatment decreases the frequency of both productively and latently infected cells via upregulation of miRNA-103. Importantly, we provide evidence that CD4+ T cells from HIV-1 elite controllers express less CCR5 than those from antiretroviral therapy-naïve progressors, an effect linked to a significant increase in miRNA-103 levels. By contributing to the control of CCR5 expression in CD4+ T cells, miRNA-103 is likely to play a key role in countering the establishment of latent HIV-1 reservoirs in vivo.

4.
J Virol ; 96(8): e0012822, 2022 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-35343766

RESUMEN

The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directs infection of the lungs and other tissues following its binding to the angiotensin-converting enzyme 2 (ACE2) receptor. For effective infection, the S protein is cleaved at two sites: S1/S2 and S2'. The "priming" of the surface S protein at S1/S2 (PRRAR685↓) [the underlined basic amino acids refer to critical residues needed for the furin recognition] by furin has been shown to be important for SARS-CoV-2 infectivity in cells and small-animal models. In this study, for the first time we unambiguously identified by proteomics the fusion activation site S2' as KPSKR815↓ (the underlined basic amino acids refer to critical residues needed for the furin recognition) and demonstrated that this cleavage was strongly enhanced by ACE2 engagement with the S protein. Novel pharmacological furin inhibitors (BOS inhibitors) effectively blocked endogenous S protein processing at both sites in HeLa cells, and SARS-CoV-2 infection of lung-derived Calu-3 cells was completely prevented by combined inhibitors of furin (BOS) and type II transmembrane serine protease 2 (TMPRSS2) (camostat). Quantitative analyses of cell-to-cell fusion and S protein processing revealed that ACE2 shedding by TMPRSS2 was required for TMPRSS2-mediated enhancement of fusion in the absence of S1/S2 priming. We further demonstrated that the collectrin dimerization domain of ACE2 was essential for the effect of TMPRSS2 on cell-to-cell fusion. Overall, our results indicate that furin and TMPRSS2 act synergistically in viral entry and infectivity, supporting the combination of furin and TMPRSS2 inhibitors as potent antivirals against SARS-CoV-2. IMPORTANCE SARS-CoV-2, the etiological agent of COVID-19, has so far resulted in >6.1 million deaths worldwide. The spike protein (S) of the virus directs infection of the lungs and other tissues by binding the angiotensin-converting enzyme 2 (ACE2) receptor. For effective infection, the S protein is cleaved at two sites: S1/S2 and S2'. Cleavage at S1/S2 induces a conformational change favoring the S protein recognition by ACE2. The S2' cleavage is critical for triggering membrane fusion and virus entry into host cells. Our study highlights the complex dynamics of interaction between the S protein, ACE2, and the host proteases furin and TMPRSS2 during SARS-CoV-2 entry and suggests that the combination of a nontoxic furin inhibitor with a TMPRSS2 inhibitor significantly reduces viral entry in lung cells, as evidenced by an average synergistic ∼95% reduction of viral infection. This represents a powerful novel antiviral approach to reduce viral spread in individuals infected by SARS-CoV-2 or future related coronaviruses.


Asunto(s)
COVID-19 , Furina , SARS-CoV-2 , Serina Endopeptidasas , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , COVID-19/patología , COVID-19/virología , Furina/metabolismo , Células HeLa , Humanos , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Serina Endopeptidasas/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Internalización del Virus
5.
Virus Evol ; 7(2): veab074, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34754512

RESUMEN

Chikungunya virus (CHIKV), an alphavirus of the Togaviridae family, is among the most medically significant mosquito-borne viruses, capable of causing major epidemics of febrile disease and severe, chronic arthritis. Identifying viral mutations is crucial for understanding virus evolution and evaluating those genetic determinants that directly impact pathogenesis and transmissibility. The present study was undertaken to expand on past CHIKV evolutionary studies through robust genome-scale phylogenetic analysis to better understand CHIKV genetic diversity and evolutionary dynamics since its reintroduction into India in 2005. We sequenced the complete genomes of fifty clinical isolates collected between 2010 and 2016 from two geographic locations, Delhi and Mumbai. We then analysed them along with 753 genomes available on the Virus Pathogen Database and Analysis Resource sampled over fifteen years (2005-20) from a range of locations across the globe and identified novel genetic variants present in samples from this study. Our analyses show evidence of frequent reintroduction of the virus into India and that the most recent CHIKV outbreak shares a common ancestor as recently as 2006.

6.
Nutrients ; 13(4)2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33919991

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Interestingly, pre-treatment of Calu-3, human lung epithelial cells, with L-carnitine tartrate led to a significant and dose-dependent inhibition of the infection by SARS-CoV-2. Infection inhibition coincided with a significant decrease in ACE2 mRNA expression levels. These data suggest that L-carnitine tartrate should be tested with appropriate trials in humans for the possibility to limit SARS-CoV-2 infection.


Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , Tratamiento Farmacológico de COVID-19 , Carnitina/administración & dosificación , Tartratos/administración & dosificación , Adulto , Anciano , Enzima Convertidora de Angiotensina 2/sangre , Animales , COVID-19/metabolismo , Carnitina/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Femenino , Furina/sangre , Furina/metabolismo , Humanos , Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Ratas , SARS-CoV-2 , Serina Endopeptidasas/sangre , Serina Endopeptidasas/metabolismo , Tartratos/farmacología , Adulto Joven
7.
Indian J Med Res ; 154(5): 669-679, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-35532585

RESUMEN

Multiple dengue virus (DENV) serotypes circulating in a geographical area most often lead to simultaneous infection of two or more serotypes in a single individual. The occurrence of such concurrent infections ranges from 2.5 to 30 per cent, reaching as high as 40-50 per cent in certain dengue hyper-endemic areas. Concurrent dengue manifests itself differently than mono-infected patients, and it becomes even more important to understand the effects of co-infecting serotypes in concurrent infections to ascertain the clinical outcomes of the disease progression and transmission. In addition, there have also been reports of concurrent DENV infections in the presence of other arboviral infections. In this review, we provide a comprehensive breakdown of concurrent dengue infections globally. Furthermore, this review also touches upon the clinical presentations during those concurrent infections categorized as mild or severe forms of disease presentation. Another aspect of this review was aimed at providing insight into the concurrent dengue incidences in the presence of other arboviruses.


Asunto(s)
Virus del Dengue , Dengue , Dengue/complicaciones , Dengue/epidemiología , Brotes de Enfermedades , Humanos , Incidencia , Serogrupo
8.
Am J Trop Med Hyg ; 102(4): 857-868, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32067624

RESUMEN

Chikungunya fever (CHIKF) is a major public health concern and is caused by chikungunya virus (CHIKV). In 2005, the virus was reintroduced into India, resulting in massive outbreaks in several parts of the country. During 2010 and 2016 outbreaks, we recruited 588 patients from a tertiary care hospital in New Delhi, India, during the acute phase of CHIKF; collected their blood and clinical data; and determined their arthralgic status 12 weeks post-onset of fever. We evaluated IgM/IgG CHIKV-binding antibodies and their neutralizing capacity, sequenced complete genomes of 21 CHIKV strains, and correlated mutations with patient sequelae status. We also performed infections in murine models using representative strains from each outbreak to evaluate differences in pathogenesis. Our screening and analysis revealed that patients of the 2016 outbreak developed earlier IgM and neutralizing antibody responses that were negatively correlated with sequelae, compared with 2010 patients. Mutations that correlated with human disease progression were also correlated with enhanced murine virulence and pathogenesis. Overall, our study suggests that the development of early neutralizing antibodies and sequence variation in clinical isolates are predictors of human sequelae.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/inmunología , Virus Chikungunya/inmunología , Brotes de Enfermedades , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Afinidad de Anticuerpos , Fiebre Chikungunya/patología , Niño , Femenino , Genoma Viral , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , India/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Adulto Joven
9.
J Ayurveda Integr Med ; 11(3): 329-335, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30685096

RESUMEN

BACKGROUND: Currently, no vaccines or modern drugs are available for dengue and chikungunya and only symptomatic relief is provided to the patients. Siddha medicine, a traditional form of indigenous medical system uses specific polyherbal formulations for the treatment of such infections with considerable success. One such polyherbal formulation for the treatment of chikungunya and dengue is Nilavembu kudineer (NVK). The mechanistic details of this drug as an antiviral for chikungunya virus (CHIKV) and dengue virus (DENV) is poorly understood. OBJECTIVES: The current study was undertaken to study the efficacy of NVK as an antiviral formulation against CHIKV and DENV. MATERIALS AND METHODS: Cytotoxicity assays (MTT) were performed to determine the role of NVK as an antiviral during chikungunya and dengue infections in the following conditions-i). post infection, ii). during active infections and iii) protective, not allowing virus infection. RESULTS: It was observed that NVK provides protection against CHIKV and DENV-2 during active infection as well can help to prevent virus infection in the cells and it mainly depends on the cellular availability of drugs for maximum protection against both the infections. CONCLUSION: Our study establishes that extraction protocols are important to ensure maximum efficacy of NVK along with the time of addition of the drug during CHIKV and DENV infections in the cells. This study provides insights to the possible mode of action of NVK in in vitro condition during CHIKV and DENV infection.

10.
Viruses ; 11(6)2019 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-31242674

RESUMEN

Chikungunya (CHIK) is a febrile arboviral illness caused by chikungunya virus (CHIKV) and has been identified in more than 60 countries across the globe. A major public health concern, the infection occurs as an acute febrile phase and a chronic arthralgic phase. The disease manifests differently in different age groups that can range from asymptomatic infection in the younger age group to a prolonged chronic phase in the elderly population. The present study was undertaken to evaluate strain-specific pathogenesis of ECSA genotype of CHIKV strains derived from clinical isolates in adult C57BL/6J mice model. The strain that was pathogenic and developed distinct acute and post-acute phase of CHIK infection was further evaluated for dose-dependent pathogenesis. Upon arriving on the optimal dose to induce clinical symptoms in the mice, the disease progression was evaluated across the acute and the post-acute phase of infection for a period of 15 days post-infection in two age groups of mice, namely eight weeks old and 20 weeks old mice groups. Biochemical, hematological, and virology attributes were measured and correlated to morbidity and linked neurotropism and limb thickness in the two age groups. Our results show that CHIKV exhibit strain-specific pathogenesis in C57BL/6J mice. Distinct dissimilarities were observed between the two age groups in terms of pathogenesis, viral clearance and host response to CHIKV infection.


Asunto(s)
Fiebre Chikungunya/patología , Fiebre Chikungunya/virología , Virus Chikungunya/crecimiento & desarrollo , Virus Chikungunya/patogenicidad , Modelos Animales de Enfermedad , Tropismo Viral , Factores de Edad , Animales , Ratones Endogámicos C57BL
11.
Virol J ; 15(1): 84, 2018 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-29751761

RESUMEN

BACKGROUND: Chikungunya virus (CHIKV) and dengue virus (DENV) are arboviruses that share the same Aedes mosquito vector, and there is much overlap in endemic areas. In India, co-infection with both viruses is often reported. Clinical manifestations of Chikungunya fever is often confused with dengue fever because clinical symptoms of both infections are similar. It is, therefore, difficult to differentiate from those of other febrile illnesses, especially dengue fever. We previously developed a CHIKV antigen detection immunochromatography (IC) rapid diagnosis kit [1]. The current study examined the efficacy of previously mentioned IC kit in India, a dengue-endemic country. METHODS: Sera from 104 CHIKV-positive (by qRT-PCR) and/or IgM-positive (ELISA) subjects collected in 2016, were examined. Fifteen samples from individuals with CHIKV-negative/DENV-positive and 4 samples from healthy individuals were also examined. Of the 104 CHIKV-positive sera, 20 were co-infected with DENV. RESULTS: The sensitivity, specificity and overall agreement of the IC assay were 93.7, 95.5 and 94.3%, respectively, using qRT-PCR as a gold standard. Also, there was a strong, statistically significant positive correlation between the IC kit device score and the CHIKV RNA copy number. The IC kit detected CHIKV antigen even in DENV-co-infected patient sera and did not cross-react with DENV NS1-positive/CHIKV-negative samples. CONCLUSIONS: The results suggest that the IC kit is useful for rapid diagnosis of CHIKV in endemic areas in which both CHIKV and DENV are circulating.


Asunto(s)
Anticuerpos Antivirales/sangre , Antígenos Virales/sangre , Fiebre Chikungunya/diagnóstico , Virus Chikungunya/inmunología , Cromatografía de Afinidad/métodos , Dengue/diagnóstico , Aedes/virología , Animales , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/virología , Virus Chikungunya/clasificación , Virus Chikungunya/genética , Virus Chikungunya/aislamiento & purificación , Coinfección , Dengue/epidemiología , Dengue/virología , Virus del Dengue/clasificación , Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Diagnóstico Diferencial , Humanos , Sueros Inmunes/química , India/epidemiología , Mosquitos Vectores/virología , Juego de Reactivos para Diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad
12.
Virusdisease ; 29(1): 32-39, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29607356

RESUMEN

Chikungunya, a viral fever caused by Aedes mosquito results in extreme morbidity in affected individuals and is a major public health concern in India. Currently, modern vaccines or formulations prescribed by physicians can only provide symptomatic relief for the pyretic and post pyretic phase of the disease. Siddha practitioners follows strict medical regimen based on traditional Indian knowledge/concepts to treat Chikungunya with considerable results. The current study was undertaken to standardize assays for the study of these siddha formulations and to check their efficacy and potential mode of action as antivirals for Chikungunya virus infection in in vitro system. Although, siddha practitioners follow a regime containing 4-6 formulations, of these Brahmanandha bairavam mathirai, a part of the regime for Chikungunya followed at National Institute of Siddha and Vishnu chakram along with Brahmanandha bairavam mathirai, a part of Thiruchergodu Regime were found of have antiviral activities. It was observed that both Vishnu chakram and Brahmanandha bairavam mathirai were equally effective in blocking Chikungunya virus from entering susceptible cells in the concentrations range of 0.0625 and 0.5 mg/ml. Additionally, it was also observed that Brahmanandha bairavam mathirai was more effective than Vishnu chakram against entry of Chikungunya in the cells. The assays used in this study provides insights to the possible mode of action of various formulations used by siddha practitioners for the treatment of Chikungunya infection.

13.
J Evid Based Integr Med ; 23: 2156587218757661, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29484895

RESUMEN

Chikungunya viral fever results in extreme morbidity and arthralgia in affected individuals. Currently, modern medicines providing symptomatic relief for the acute febrile phase and the chronic arthritic phase are only options available. Traditional Indian medical system, however, uses specific formulations for treatment of this infection; one such polyherbal formulation used to treat the postpyretic phase of chikungunya is amukkara choornam. The current study was undertaken to study the efficacy of amukkara choornam in the treatment of chikungunya in C57BL/6J mice. The formulation when administered to chikungunya-infected mice relieved morbidity and joint swelling. Analysis of virus clearance in brain and joint tissues on formulation treatment revealed a direct correlation of viral load in brain to morbidity during infection; likewise, joint swelling receded prior to complete viral clearance explaining possible immunomodulatory effect of amukkara choornam. This study provides insight into the possible mode of action of amukkara choornam during chikungunya.


Asunto(s)
Artralgia/tratamiento farmacológico , Fiebre Chikungunya/tratamiento farmacológico , Virus Chikungunya/fisiología , Extractos Vegetales/administración & dosificación , Withania/química , Animales , Artralgia/virología , Fiebre Chikungunya/virología , Virus Chikungunya/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Femenino , Humanos , India , Masculino , Medicina Tradicional , Ratones , Ratones Endogámicos C57BL , Morbilidad , Carga Viral/efectos de los fármacos
14.
Sci Rep ; 7(1): 17666, 2017 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-29247247

RESUMEN

Arboviruses that replicate in mosquitoes activate innate immune response within mosquitoes. Regulatory non-coding microRNAs (miRNA) are known to be modulated in mosquitoes during chikungunya infection. However, information about targets of these miRNAs is scant. The present study was aimed to identify and analyze targets of miRNAs that are regulated during chikungunya virus (CHIKV) replication in Aedes aegypti cells and in the mosquito. Employing next-generation sequencing technologies, we identified a total of 126 miRNAs from the Ae. aegypti cell line Aag2. Of these, 13 miRNAs were found to be regulated during CHIKV infection. Putative targets of three of the most significantly regulated miRNAs- miR-100, miR-2b and miR-989 were also analyzed using quantitative PCRs, in cell lines and in mosquitoes, to validate whether they were the targets of the miRNAs. Our study expanded the list of miRNAs known in Ae. aegypti and predicted targets for the significantly regulated miRNAs. Further analysis of some of these targets revealed that ubiquitin-related modifier is a target of miRNA miR-2b and plays a significant role in chikungunya replication.


Asunto(s)
Aedes/genética , Virus Chikungunya/genética , MicroARNs/genética , Ubiquitina/genética , Replicación Viral/genética , Aedes/virología , Animales , Línea Celular , Fiebre Chikungunya/virología , Mosquitos Vectores/genética
15.
Clin Infect Dis ; 65(1): 133-140, 2017 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-28379375

RESUMEN

Background: Chikungunya fever (CHIK) is a major public health concern in India. Characterized by acute fever with joint pain and swelling, most patients recover from this self-limiting illness in 7-10 days, with cessation of joint pain post-acute episode. However, in some patients, joint pain persists, lasting for months or even years. The precise correlates to the chronic phase of this debilitating illness and/or this remarkable heterogeneity in disease manifestation are poorly understood. Methods: We evaluated 572 chikungunya patients from India who were recruited on the basis of positive real-time polymerase chain reaction and/or CHIK virus immunoglobulin (IgM) after receiving consent. Arthralgic conditions were monitored using visual analog score (VAS) 12 weeks after onset of fever in 130 patients. Initial viral load, IgG, and initial neutralization response were assayed and correlated with clinical and VAS information in 40 patients. Results: Our extensive screening revealed that patients with higher initial viral loads during the acute phase of illness had poor prognosis at the post-acute phase with more restricted joint movement and higher VAS. Additionally, patients who showed early seroconversion to neutralizing IgG responses had better prognosis, as many of these patients did not manifest restricted joint movements at the post-acute phase. Conclusions: Our study sheds light on chikungunya disease with respect to disease progression and assesses clinical, virological, and serological parameters of chikungunya disease severity. Importantly, it reveals that initial high viral load and neutralizing IgG response may function in a seemingly contrasting manner to negatively or positively dictate disease outcome.


Asunto(s)
Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/inmunología , Virus Chikungunya , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/virología , Virus Chikungunya/genética , Virus Chikungunya/inmunología , Estudios de Cohortes , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Carga Viral , Adulto Joven
16.
Biochem Biophys Res Commun ; 492(4): 608-616, 2017 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-28189673

RESUMEN

Dengue and Chikungunya are viral infections that are a major public health hazard in recent times. Both these infections are caused by RNA viruses termed arboviruses owing to their requirement of an arthropod vector to get transmitted to vertebrate hosts. Apart from sharing a common vector, namely Aedes mosquitoes, these infections are also characterized by overlapping clinical presentations and are known to exist as co-infection. The present review traces the history and evolution of co-infection across the globe and provides specific compilation of the scenario in India. Furthermore, clinical manifestations during co-infection are discussed. Lastly, up-to-date information with respect to vector behaviour during co-infection both under laboratory conditions and in natural Aedes populations is reviewed.


Asunto(s)
Aedes/virología , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/virología , Coinfección/epidemiología , Coinfección/virología , Dengue/epidemiología , Dengue/virología , Animales , Virus Chikungunya/fisiología , Comorbilidad , Virus del Dengue/fisiología , Brotes de Enfermedades/estadística & datos numéricos , Humanos , Insectos Vectores/virología , Prevalencia , Factores de Riesgo
17.
F1000Res ; 6: 1601, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29333236

RESUMEN

Background: Chikungunya fever presents as a high-grade fever during its acute febrile phase and can be prolonged for months as chronic arthritis in affected individuals. Currently, there are no effective drugs or vaccines against this virus. The present study was undertaken to evaluate protein-ligand interactions of all chikungunya virus (CHIKV) proteins with natural compounds from a MolBase library in order to identify potential inhibitors of CHIKV. Methods: Virtual screening of the natural compound library against four non-structural and five structural proteins of CHIKV was performed. Homology models of the viral proteins with unknown structures were created and energy minimized by molecular dynamic simulations. Molecular docking was performed to identify the potential inhibitors for CHIKV. The absorption, distribution, metabolism and excretion (ADME) toxicity parameters for the potential inhibitors were predicted for further prioritization of the compounds. Results: Our analysis predicted three compounds, Catechin-5-O-gallate, Rosmarinic acid and Arjungenin, to interact with CHIKV proteins; two (Catechin-5-O-gallate and Rosmarinic acid) with capsid protein, and one (Arjungenin) with the E3. Conclusion: The compounds identified show promise as potential antivirals, but further in vitro studies are required to test their efficacy against CHIKV.

18.
Virol J ; 13: 86, 2016 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-27251040

RESUMEN

BACKGROUND: RNA viruses are characterized by high rate of mutations mainly due to the lack of proofreading repair activities associated with its RNA-dependent RNA-polymerase (RdRp). In case of arboviruses, this phenomenon has lead to the existence of mixed population of genomic variants within the host called quasi-species. The stability of strains within the quasi-species lies on mutations that are positively selected which in turn depend on whether these mutations are beneficial in either or both hosts. Coevolution of amino acids (aa) is one phenomenon that leads to establishment of favorable traits in viruses and leading to their fitness. RESULTS: Fourteen CHIKV clinical samples collected over three years were subjected to RT-PCR, the four non-structural genes amplified and subjected to various genetic analyses. Coevolution analysis showed 30 aa pairs coevolving in nsP1, 23 aa pairs coevolving in nsP2, 239 in nsP3 and 46 aa coevolving pairs in nsP4 when each non-structural protein was considered independently. Further analysis showed that 705 amino acids pairs of the non-structural polyproteins coevolved together with a correlation coefficient of ≥0.5. Functional relevance of these coevolving amino acids in all the nonstructural proteins of CHIKV were predicted using Eukaryotic Linear Motifs (ELMs) of human. CONCLUSIONS: The present study was undertaken to study co-evolving amino acids in the non-structural proteins of chikungunya virus (CHIKV), an important arbovirus. It was observed that several amino acids residues were coevolving and shared common functions.


Asunto(s)
Fiebre Chikungunya/virología , Virus Chikungunya/genética , Evolución Molecular , Proteínas no Estructurales Virales/genética , Aminoácidos/genética , Virus Chikungunya/aislamiento & purificación , Humanos , Análisis de Secuencia de ADN
19.
Acta Trop ; 162: 46-55, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27282096

RESUMEN

Aedes aegypti and Aedes albopictus are principal vectors for the transmission of chikungunya virus (CHIKV). India is a hub for both dengue and chikungunya infections and there are several reports of co-infection of dengue and chikungunya virus in the clinical scenario. The present pilot entomological survey was conducted to evaluate vertical transmission of CHIKV in Aedes field populations. Aedes immature (larvae and pupae) collection was done in 2012, over a period of six months from selected sites in Delhi and Haryana, India. The immatures collected were reared for adult emergence and species identification was done. A. aegypti male and female mosquitoes were separated and pooled collection spot-wise, RNA extracted and RT PCR performed to test for the presence of CHIKV in the pools. Container index (CI) and minimum infection rate (MIR) were estimated. From study areas that tested positive for CHIKV, adult collections were made and females upon feeding on uninfected blood in laboratory were allowed to lay eggs. The progeny that emerged from these field-collected mothers were tested for CHIKV presence. Our pilot survey showed the existence of A. aegypti population even during peak summer season in a few foci which eventually helped the mosquitoes to tide over adverse environmental conditions and with the start of rainfall, the population exploded within a short period of time. Immatures collected from field and progeny of adults collected from the field were CHIKV positive demonstrating the presence of vertical transmission of chikungunya virus in field population of A. aegypti. The present study further demonstrates the importance of identifying permanent breeding sites for proper Aedes species control.


Asunto(s)
Aedes/virología , Fiebre Chikungunya/transmisión , Fiebre Chikungunya/virología , Virus Chikungunya/clasificación , Virus Chikungunya/genética , Transmisión Vertical de Enfermedad Infecciosa , Insectos Vectores/virología , Adulto , Aedes/clasificación , Animales , Fiebre Chikungunya/epidemiología , Femenino , Humanos , India , Insectos Vectores/clasificación , Larva/virología , Masculino , Pupa/virología , Estaciones del Año
20.
PLoS Negl Trop Dis ; 8(1): e2616, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24421911

RESUMEN

BACKGROUND: Application of genomics and Next Generation sequencing has led to the identification of new class of cellular functional molecules, namely, small RNAs. Of the several classes of ncRNAs (non-coding RNA), microRNAs have been demonstrated to exert determinative influence on various cellular processes. It is becoming abundantly clear that host/vector/pathogen encoded microRNAs impact eventual pathogenesis. In this context, the participation of vector based microRNAs in disease transmission and pathogen development is being investigated intensively. A few studies have highlighted the role of vector encoded microRNAs in pathogen infection. We conducted this study to evaluate the role of host miRNAs upon CHIKV (Chikungunya Virus) infection in an important vector, Aedes albopictus. FINDINGS: We identified 88 and 79 known miRNAs in uninfected and CHIKV infected Ae. albopictus Singh's cell line respectively. We further identified nine novel miRNAs in Ae. albopictus. Comparison of the two libraries revealed differential expression of 77 common miRNAs between them. CHIKV infection specifically altered the miRNA profile of a specific set of eight miRNAs. Putative targets of these regulated miRNAs were identified and classified into their pathways. CONCLUSIONS: In our study we have identified and described the profiles of various miRNAs upon CHIKV infection in Ae. albopictus. This investigation provides an insight about cellular modification by miRNAs during CHIKV infection and the results provide leads for identifying potential candidates for vector based antiviral strategies.


Asunto(s)
Aedes/genética , Aedes/virología , Virus Chikungunya/crecimiento & desarrollo , Perfilación de la Expresión Génica , Interacciones Huésped-Patógeno , Insectos Vectores , MicroARNs/biosíntesis , Animales , Secuenciación de Nucleótidos de Alto Rendimiento , MicroARNs/genética
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