Hepatitis & Nanomedicine: A Review

In the year 1989, hepatitis C virus (HCV) was specifically established as causative factor accountable for many more occurrences of hepatitis. It's a chronic disease which majorly contributes to Carcinoma and Cirrhosis. The hepatitis C virus belongs a family Flaviviridae (+) enveloped ssRNA virus. It has been described that seven major genotypes of HCV and their subtypes (a, b). Around 3 percent among global residents has been infected by HCV. HCV Transmission is frequently associated with direct percutaneous blood contact, via blood transfusions, health-related injections and substance use injections. Several new therapies have been developed to treat HCV, such as polyethylene glycol (PEG)-ylated interferon / ribavirin, antivirals acting directly and antivirals targeting the host. Despite progress in anti-HCV therapy, there is still an urgent need for new approaches of targeted drug delivery systems using nanomedicine which are affordable and reliable. Nanotechnology has the ability to play a pivotal role in lowering viral load levels and drug-resistant HCV by targeting drugs directly to the disease site. In addition to tissue targeting, a wide variety of drugs need to be administered intracellularly to achieve a therapeutic effect in the organ affected. The contribution of nanoparticles as a promising delivery mechanism for HCV immunizing, diagnostic and therapeutic agents and there latest developments of drug carriers as well as their role in anti-HCV therapy were addressed in this review.

Increasing number of secondary dengue cases: a concern

ackground: Dengue fever is caused by mosquito borne arbovirus of family Flaviviridae, Aedes agypti as the principle vector. In the recent past Delhi has witnessed several outbreaks affecting thousands of individuals and many of them get re-infected during subsequent years forming a bulk of secondary dengue cases putting them at risk of developing severe dengue.Methods: A total of 150 serum samples from suspected dengue cases were tested for dengue fever by NS-1 antigen and IgM antibody enzyme-linked immunosorbent assay (ELISA) followed by categorization into primary and secondary dengue using IgG avidity ELISA.Results: Out of total 150 clinically suspected dengue cases, 56 were positive either by Dengue NS-1 antigen or dengue IgM antibody or both. On the basis of dengue IgG avidity ELISA among 56 diagnosed dengue cases, 30 (53.57%) were found to be of secondary dengue.Conclusions: There is increasing trend of dengue cases in Delhi since past one decade. Being hyper-endemic area for dengue, more than 25% population have been reported to have past infection of dengue. Due to increased prevalence and simultaneous circulation of more than one serotypes, number of secondary dengue cases is also increasing. Since majority of severe dengue cases are associated with secondary dengue, early diagnosis and treatment can significantly reduce the fatal outcome. Thus, avidity testing for IgG antibody becomes an important tool.

Phylogeny of Culex theileri virus flavivirus in Spain, Myanmar, Portugal and Turkey

Objective: To study the genetic diversity of Culex theileri flavivirus and the spread of this virus among Spain, Portugal and Turkey. Methods: A database consisting of 55 sequences of the NS5/3'UTR region of Culex theileri flavivirus group downloaded from GenBank were aligned and manual edited with Bioedit. ModelTest v. 3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data. Maximum likelihood analysis was performed using MEGA7. The phylogenetic signal of the dataset was investigated by the likelihood mapping analysis. Results: The phylogenetic tree showed three clusters. Myanmar sequences clusterd together with Turkish sequences, Spain and Portugal strains grouped together and two Turkish sequences grouped separately. Selective pressure analysis showed a moderate percentage of sites (22.5%) under pervasive negative selection and only 1% under pervasive positive selection. The sites subject to selective pressure in CTFV RdRp NS5 fragments have been located onto the predicted three-dimensional structure. Conclusions: Phylogenetic and evolutionary analysis can be an important tool for understanding the evolutionary impact of the probable contemporary existence between non-pathogenic and pathogenic flaviviruses among these vectors.

Phylogeny of Culex theileri virus flavivirus in Spain, Myanmar, Portugal and Turkey

Objective: To study the genetic diversity of Culex theileri flavivirus and the spread of this virus among Spain, Portugal and Turkey. Methods: A database consisting of 55 sequences of the NS5/3'UTR region of Culex theileri flavivirus group downloaded from GenBank were aligned and manual edited with Bioedit. ModelTest v. 3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data. Maximum likelihood analysis was performed using MEGA7. The phylogenetic signal of the dataset was investigated by the likelihood mapping analysis. Results: The phylogenetic tree showed three clusters. Myanmar sequences clusterd together with Turkish sequences, Spain and Portugal strains grouped together and two Turkish sequences grouped separately. Selective pressure analysis showed a moderate percentage of sites (22.5%) under pervasive negative selection and only 1% under pervasive positive selection. The sites subject to selective pressure in CTFV RdRp NS5 fragments have been located onto the predicted three-dimensional structure. Conclusions: Phylogenetic and evolutionary analysis can be an important tool for understanding the evolutionary impact of the probable contemporary existence between non-pathogenic and pathogenic flaviviruses among these vectors.

Progress in the study of the association between the lipid droplets and hepatitis C virus life cycle / 药学学报

Lipid droplets (LDs) are ubiquitous dynamic organelles that store and supply lipids in all eukaryotic and some prokaryotic cells for energy metabolism, membrane synthesis and production of essential lipid-derived molecules. There is increasing evidence that hepatitis C virus (HCV) has co-evolved due to its lack of lipid biosynthetic pathways to utilize host lipid metabolic pathways to establish a suitable environment for virus proliferation and obtain the necessary components, eventually promote the assembly and transportation of virus. In this review, we outline the relationship between HCV life cycle and lipid droplet biosynthesis and metabolism, with the aim to discover potential antiviral targets for development of new therapeutic interventions.

Hemofagocitosis secundaria a dengue / Hemophagocytosis secondary to dengue fever

La infección por el virus del dengue constituye un problema de salud pública mundial. Causada por un virus de la familia Flaviviridae, presenta un amplio espectro clínico, desde formas asintomáticas frecuentes hasta las formas graves de fiebre hemorrágica y shock por fuga capilar. Existen cuatro serotipos; los serotipos 2 y 3 están asociados a las formas graves de la enfermedad. El diagnóstico definitivo de infección por dengue depende del aislamiento del virus en sangre, de la detección del antígeno viral o el ARN viral en suero o tejido, o detección de anticuerpos específicos. El síndrome hemofagocítico se produce ante la desregulación del sistema inmune que lleva a la activación macrofágica descontrolada, y se manifiesta con alteraciones clínicas, hematológicas, bioquímicas e histológicas. La asociación entre ambas entidades se encuentra descripta como una forma inusual y grave de presentación que responde a la tormenta de citocinas liberadas durante la enfermedad. Presentamos el caso de un paciente adulto con dengue, hemofagocitosis y valores inusualmente elevados de ferritina en sangre que evolucionó favorablemente con tratamiento de soporte.

Dengue virus infection constitutes a major public health problem worldwide. It is caused by a virus belonging to the Flaviviridae family. It produces a wide range of clinical presentations, from asymptomatic infection to severe forms of the disease with hemorrhagic fever or shock secondary to capillary leak syndrome. Four serotypes have been described; serotype 2 and serotype 3 are associated with the most severe forms of the disease. The diagnosis is based on laboratory tests aimed to detect antibodies, viral RNA, or antigens in serum. The hemophagocytic syndrome is generated by a dysfunction of the immune system with clinical, hematological, biochemical and histological manifestations. The association between these two entities is described as an unusual and severe presentation of dengue fever. We present a case of an adult patient with this association and very high blood levels of ferritin, who responded favorably to supportive care.

Improved reverse transcription-polymerase chain reaction assay for the detection of flaviviruses with semi-nested primers for discrimination between dengue virus serotypes and Zika virus

BACKGROUND The genus Flavivirus includes a variety of medically important viruses, including dengue virus (DENV) and Zika virus (ZIKV), which are most prevalent in Brazil. Because the clinical profile of patients affected by different DENV serotypes or ZIKV may be similar, the development of new methods that facilitate a rapid and accurate diagnosis is crucial. OBJECTIVES The current study aimed to develop an improved reverse transcription-polymerase chain reaction (RT-PCR) protocol for universal detection of flaviviruses by using semi-nested primers that discriminate between DENV serotypes and ZIKV. METHODS The bioinformatics workflow adopted for primer design included: (1) alignment of 1,442 flavivirus genome sequences, (2) characterisation of 27 conserved regions, (3) generation of a primer set comprising 77 universal primers, and (4) selection of primer pairs with greatest coverage and specificity. Following primer design, the reaction was validated in vitro. The same approach was applied to the design of primers specific for DENV and ZIKV, using a species-specific sequence database. FINDINGS The new assay amplified an 800-806 nt variable region of the NS5 gene and allowed discrimination of virtually all flavivirus species using reference-sequence comparison. The 800-806 nt fragment was validated as a template for a semi-nested multiplex PCR using five additional primers for the detection of DENV and ZIKV. These primers were designed to generate amplicons of different sizes, allowing differentiation of the four serotypes of DENV, and ZIKV using agarose gel electrophoresis. MAIN CONCLUSIONS The bioinformatics pipeline allowed efficient primer design, making it possible to identify the best targets within the coding region of the NS5 protein. The multiplex system proved effective in differentiation of DENV1-4 and ZIKV on a 2% agarose gel. The possibility of discriminating DENV serotypes and ZIKV in the same reaction provided a faster result consuming less sample. In addition, this simplified approach ensured the reduction of the cost per analysis.

Research progress on characteristics of Zika virus and its infection in human / 中华临床感染病杂志

Zika virus was named after the Ugandan forest where it was first isolated in a rhesus monkey in 1947, and the first confirmed human case was reported in 1954 in Nigeria.The incidence of Zika virus disease is very low.In the year 2014, Zika virus infection appeared in the Western hemisphere, and then the virus rapidly spread to Americas, Caribbean and Pacific island countries.Currently more than 30 countries have reported Zika virus infection, and officials estimate there will be 4 million Zika infections. Zika virus disease is a self-limited disease with mild symptoms, however, Zika virus is neuroinvasive.It can be transmitted to infants from mothers who infected in the early months of pregnancy, and may cause microcephaly, retinae macula and optic nerve abnormalities.Guillain-Barré syndrome is also found as a complication of Zika virus infection in some cases.Zika virus is mainly transmitted by aedes mosquito, and no vaccine is available at present, so the prevention of its infection is difficult.This paper reviews the research progress of Zika virus infection, including virus characteristics, epidemiology and clinical feature of Zika infection in human.

Dos nuevos registros de vectores potenciales de Fiebre Amarilla selvática y Mayaro para el Ecuador / Two new records of potential Sylvan Yellow Fever and Mayaro species vectors from Ecuador

Se registran por primera vez en el Ecuador dos especies de mosquitos (Diptera: Culicidae), vectores potenciales de los virus de la Fiebre Amarilla y Mayaro. Sabethes amazonicus Gordon and Evans y Haemagogus anastasionis Dyar fueron colectados en fase adulta en una localidad de la provincia de Zamora-Chinchipe, en la cual se han presentado casos de Fiebre Amarilla selvática con anterioridad. Este hallazgo muestra la importancia de profundizar los estudios de linea base de vectores en el país, distribución geográfica y aspectos ecológicos y su posible relación epidemiológica con enfermedades emergentes y re-emergentes.

Two new records of mosquitoes (Diptera: Culicidae) are presented from Ecuador, and both potential vectors of yellow fever virus and Mayaro. Sabethes amazonicus Gordon and Evans and Haemagogus anastasionis Dyar adults were collected in a locality in the province of Zamora-Chinchipe, in which there have been cases of yellow fever previously. This finding shows the importance of further studies of baseline vector in the country, geographical distribution and ecological aspects and possible epidemiological link with emerging and re-emerging diseases.

Dengue in India.

Dengue virus belongs to family Flaviviridae, having four serotypes that spread by the bite of infected Aedes mosquitoes. It causes a wide spectrum of illness from mild asymptomatic illness to severe fatal dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Approximately 2.5 billion people live in dengue-risk regions with about 100 million new cases each year worldwide. The cumulative dengue diseases burden has attained an unprecedented proportion in recent times with sharp increase in the size of human population at risk. Dengue disease presents highly complex pathophysiological, economic and ecologic problems. In India, the first epidemic of clinical dengue-like illness was recorded in Madras (now Chennai) in 1780 and the first virologically proved epidemic of dengue fever (DF) occurred in Calcutta (now Kolkata) and Eastern Coast of India in 1963-1964. During the last 50 years a large number of physicians have treated and described dengue disease in India, but the scientific studies addressing various problems of dengue disease have been carried out at limited number of centres. Achievements of Indian scientists are considerable; however, a lot remain to be achieved for creating an impact. This paper briefly reviews the extent of work done by various groups of scientists in this country.

Vigilância sorológica para arbovírus em Juruti, Pará, Brasil / Serological survey for arboviruses in Juruti, Pará State, Brazil

O objetivo foi avaliar a prevalência de anticorpos para arbovírus na área de influência do Projeto Juruti antes da exploração mineral local. Foram examinados 1.597 soros humanos e 85 de animais silvestres. A pesquisa de anticorpos foi realizada pelo teste de inibição da hemaglutinação contra antígenos dos arbovírus mais prevalentes na Amazônia brasileira e IgM-ELISA para dengue e febre amarela. Soros humanos inibidores da hemaglutinação positivos para Mayaro e Oropouche foram também testados por IgM-ELISA. Anticorpos inibidores da hemaglutinação para alfavírus, orthobunyavirus e/ou flavivírus foram detectados, sendo 28,7 por cento reações monotípicas. Infecções recentes para Oropouche (n = 23), Mayaro (n = 5), e dengue (n = 20) foram confirmadas por IgM-ELISA. A prevalência de anticorpos inibidores da hemaglutinação em soros de animais silvestres foi de 8,2 por cento para flavivírus. Os resultados obtidos mostram que houve circulação ativa dos vírus Mayaro, Oropouche e dengue no período do estudo em humanos em Juruti, Pará, Brasil, e de diversos arbovírus em animais silvestres, indicando presença desses vírus em áreas do Município de Juruti.

This study aimed to measure the prevalence of antibodies to arboviruses in the area affected by the Juruti Project before local mining operations. A total of 1,597 human and 85 wild animal sera were examined, using the hemagglutination inhibition test against 19 antigens from the most prevalent arboviruses in the Brazilian Amazon and IgM-ELISA for dengue and yellow fever. Positive sera for Mayaro and Oropouche viruses were also tested by IgM-ELISA. Prevalence of hemagglutination inhibition antibodies to alphaviruses, flaviviruses, and orthobunyaviruses in humans was 28.7 percent, while for wild animals it was 8.2 percent for flaviviruses. Recent infections based on presence of IgM was confirmed for Mayaro (n = 5), Oropouche (n = 23), and dengue (n = 20). The results showed active circulation of the dengue, Mayaro, and Oropouche viruses in Juruti, as well as flaviviruses in wild animals, suggesting the circulation of these viruses in the Municipality of Juruti.