scholarly journals Intra-Serotype Polyprotein Variation and its Effect on Antigenicity of Dengue Virus

2021 ◽  
Vol 53 (01) ◽  
pp. 27-34
Author(s):  
Ipsita Chanda ◽  

Dengue virus is a mosquito-borne human pathogen, causing disease that ranges from mild febrile illness to life-threatening hemorrhage fever/ shock syndrome. The altered antigenicity and virulence in the dengue virus, resulting from the accumulation and fixation of the favorable mutations in the genome, is the cause of concern nowadays. The present study focuses on the comparative study of polyproteins of viral strains within each dengue serotype to understand the trend of intra-serotype polyprotein variation and its effect on the antigenicity. Polyprotein sequences of viral strains in each serotype were investigated using multivariate statistical analysis, phylogenetic analysis and multiple sequence alignment methods. Epitope prediction was done by Bepipred-1.0 server and experimental epitope data were extracted from Immune Epitope Database with BLAST search. The study reveals that the polyproteins of viral strains of a serotype have variable amino acid composition that corresponds to the geographical regions of origin. This compositional variation has occurred due to the presence of polymorphic residues at different positions along the polyprotein sequence. The polymorphic residues have also been identified at epitope regions of structural proteins as well as NS1 of viral strains, possessing dissimilar physicochemical properties and occupy surface accessible positions. These positions on epitopes with polymorphic, dissimilar and surface accessible residues might act as putative sites for generation of antigenic variation among viral strains of a serotype of different geographical origin. Thus, these polymorphic residue positions on epitopes might be considered as putative target for development of drug or vaccine, in future.

2012 ◽  
Vol 141 (9) ◽  
pp. 1816-1822 ◽  
Author(s):  
E. HUHTAMO ◽  
G. COMACH ◽  
G. SIERRA ◽  
D. E. CAMACHO ◽  
T. SIRONEN ◽  
...  

SUMMARYDengue is a mosquito-borne disease caused by four closely related dengue virus (genusFlavivirus) serotypes (DENV-1–4). The clinical outcomes vary from mild febrile illness to life-threatening haemorrhagic manifestations. DENVs are endemic in the tropics and subtropics globally and currently no specific treatment or vaccines are available. In Venezuela, the American-Asian genotype of DENV-2 is the most prevalent and has been associated with severe disease outcomes. We aimed to follow-up the molecular epidemiology of DENV-2 in Venezuela to investigate if the evolution of the virus has remained the same throughout time or if the same dynamics documented in Brazil (hyperendemic co-circulation) also occurred. The results show that whereas the epidemiology of DENV in several endemic areas is characterized by serotype replacements through time, in Venezuela the American-Asian genotype DENV-2 has evolved into several genetic lineages and has remained in hyperendemic co-circulation with the other serotypes.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Saber Yezli

Abstract Human exposure to a hot environment may result in various heat-related illnesses (HRIs), which range in severity from mild and moderate forms to life-threatening heatstroke. The Hajj is one of the largest annual mass gatherings globally and has historically been associated with HRIs. Hajj attracts over two million Muslim pilgrims from more than 180 countries to the holy city of Makkah, Kingdom of Saudi Arabia. Several modifiable and non-modifiable factors render Hajj pilgrims at increased risk of developing HRIs during Hajj. These include characteristics of the Hajj, its location, population, and rituals, as well as pilgrims’ knowledge of HRIs and their attitude and behavior. Makkah is characterized by a hot desert climate and fluctuating levels of relative humidity. Pilgrims are very diverse ethnically and geographically, with different adaptations to heat. Significant proportions of the Hajj population are elderly, obese, and with low levels of fitness. In addition, many have underlying health conditions and are on multiple medications that can interfere with thermoregulation. Other factors are inherent in the Hajj and its activities, including crowding, physically demanding outdoor rituals, and a high frequency of infection and febrile illness. Pilgrims generally lack awareness of HRIs, and their uptake of preventive measures is variable. In addition, many engage in hazardous behaviors that increase their risk of HRIs. These include performing rituals during the peak sunshine hours with no sun protection and with suboptimal sleep, nutrition, and hydration, while neglecting treatment for their chronic conditions. HRIs preventive plans for Hajj should incorporate measures to address the aforementioned factors to reduce the burden of these illnesses in future Hajj seasons. Lessons from the Hajj can be used to inform policy making and HRIs preventive measures in the general population worldwide.


2016 ◽  
Vol 54 (4) ◽  
pp. 860-867 ◽  
Author(s):  
Jesse J. Waggoner ◽  
Benjamin A. Pinsky

Zika virus (ZIKV) is anAedesmosquito-borne flavivirus that emerged in Brazil in 2015 and then rapidly spread throughout the tropical and subtropical Americas. Based on clinical criteria alone, ZIKV cannot be reliably distinguished from infections with other pathogens that cause an undifferentiated systemic febrile illness, including infections with two common arboviruses, dengue virus and chikungunya virus. This minireview details the methods that are available to diagnose ZIKV infection.


Author(s):  
Sujay Ray ◽  
Arundhati Banerjee

Toll-Like Receptor-4 (TLR4) senses life-threatening Ebola virus Glycoprotein (GP) and produces pro-inflammatory cytokines, resulting in lethal Ebola virus infections. GP2-subunit of Ebola promotes viral entry via membrane fusion. The present study models, optimizes and demonstrates the 3D monomer of the responsible human protein. The essential residue (studied from wet-laboratory research) was observed to be functionally conserved from multiple-sequence alignment. Thus, after performing point-mutation, the mutant protein was satisfactorily re-modelled; keeping its functionality preserved. Comparable residual participation in GP2 and each of the proteins was examined, individually. Stability of the proteins and protein-GP2 complexes on mutation; were discerned via energy calculations, solvent-accessibility area and conformational switching, with supportive statistical significances. Therefore, this probe paves a pathway to examine the weaker interaction of the stable mutated human protein with Ebola GP2 protein, thereby defending the Ebola viral entry.


2020 ◽  
Vol 14 (1) ◽  
pp. e0007971
Author(s):  
Elba Caraballo ◽  
B. Katherine Poole-Smith ◽  
Kay M. Tomashek ◽  
Brenda Torres-Velasquez ◽  
Luisa I. Alvarado ◽  
...  

Author(s):  
Dibyendu Sengupta ◽  
Jane C. Burns ◽  
Andrew Kahn ◽  
Alison L. Marsden

Kawasaki disease (KD) is an acute febrile illness that can result in life threatening coronary artery aneurysms in up to 25% of untreated patients. These aneurysms put patients at risk for thrombus formation, myocardial infarction and sudden death. Currently, clinical decisions are made based on anatomy alone, with aneurysm diameter > 8mm as the arbitrary cutoff for anticoagulation therapy, despite a lack of evidence for this choice. We postulate that patient specific hemodynamics may be a better predictor for the risk of thrombosis than maximum diameter alone. To quantify hemodynamics, we performed computational fluid dynamics (CFD) simulations using patient specific models with custom coronary boundary conditions.


1990 ◽  
Vol 3 (4) ◽  
pp. 376-396 ◽  
Author(s):  
E A Henchal ◽  
J R Putnak

Dengue, a major public health problem throughout subtropical and tropical regions, is an acute infectious disease characterized by biphasic fever, headache, pain in various parts of the body, prostration, rash, lymphadenopathy, and leukopenia. In more severe or complicated dengue, patients present with a severe febrile illness characterized by abnormalities of hemostasis and increased vascular permeability, which in some instances results in a hypovolemic shock. Four distinct serotypes of the dengue virus (dengue-1, dengue-2, dengue-3, and dengue-4) exist, with numerous virus strains found worldwide. Molecular cloning methods have led to a greater understanding of the structure of the RNA genome and definition of virus-specific structural and nonstructural proteins. Progress towards producing safe, effective dengue virus vaccines, a goal for over 45 years, has been made.


2018 ◽  
Vol 16 (03) ◽  
pp. 1840017 ◽  
Author(s):  
Amr Alhossary ◽  
Yaw Awuni ◽  
Chee Keong Kwoh ◽  
Yuguang Mu

Dengue fever is a febrile illness caused by Dengue Virus, which belongs to the Flaviviridae family. Among its proteome, the nonstructural protein 5 (NS5) is the biggest and most conserved. It has a primer-independent RNA-dependent RNA polymerase (RdRp) domain at its C-Terminus. Zou et al. studied the biological relevance of the two conserved cavities (named A and B) within the NS5 proteins of dengue virus (DENV) and West Nile Virus (WNV) using mutagenesis and revertant analysis and found four mutations located at cavity B having effects on viral replication. They recommended Cavity B, but not Cavity A as a potential target for drugs against flavivirus RdRp. In this study, we virtually screened the MayBridge drug fragments dataset for potential small molecule binders of cavity B using both AutoDock Vina, the standard docking tool, and QuickVina 2, our previously developed tool. We selected 16 fragments that appeared in the top 100 docking results of each of the representative structures of NS5. Visual inspection suggests that they have reasonable binding poses. The 16 predicted fragments are plausible drug candidates and should be considered for further validation, optimization, and linking to come up with a suitable inhibitor of dengue virus.


2014 ◽  
Vol 143 (2) ◽  
pp. 412-418 ◽  
Author(s):  
P. V. BARDE ◽  
B. K. KORI ◽  
M. K. SHUKLA ◽  
P. K. BHARTI ◽  
G. CHAND ◽  
...  

SUMMARYDengue is regarded as the most important arboviral disease. Although sporadic cases have been reported, serotypes responsible for outbreaks have not been identified from central India over the last 20 years. We investigated two outbreaks of febrile illness, in August and November 2012, from Korea district (Chhattisgarh) and Narsinghpur district (Madhya Pradesh), respectively. Fever and entomological surveys were conducted in the affected regions. Molecular and serological tests were conducted on collected serum samples. Dengue-specific amplicons were sequenced and phylogenetic analyses were performed. In Korea and Narsinghpur districts 37·3% and 59% of cases were positive, respectively, for dengue infection, with adults being the worst affected. RT–PCR confirmed dengue virus serotype 1 genotype III as the aetiology. Ninety-six percent of infections were primary. This is the first time that dengue virus 1 outbreaks have been documented from central India. Introduction of the virus into the population and a conducive mosquitogenic environment favouring increased vector density caused the outbreak. Timely diagnosis and strengthening vector control measures are essential to avoid future outbreaks.


2019 ◽  
Vol 3 ◽  
pp. 44 ◽  
Author(s):  
Mary Dias ◽  
Chitra Pattabiraman ◽  
Shilpa Siddappa ◽  
Malali Gowda ◽  
Anita Shet ◽  
...  

Background: Mosquito-borne flaviviruses, such as dengue and Japanese encephalitis virus (JEV), cause life-threatening diseases, particularly in the tropics. Methods: Here we performed unbiased metagenomic sequencing of RNA extracted from the serum of four patients and the plasma of one patient, all hospitalized at a tertiary care centre in South India with severe or prolonged febrile illness, together with the serum from one healthy control, in 2014. Results: We identified and assembled a complete dengue virus type 3 sequence from a case of severe dengue fever. We also identified a small number of JEV sequences in the serum of two adults with febrile illness, including one with severe dengue. Phylogenetic analysis revealed that the dengue sequence belonged to genotype III. It has an estimated divergence time of 13.86 years from the most highly related Indian strains. In total, 11 amino acid substitutions were predicted for this strain in the antigenic envelope protein, when compared to the parent strain used for development of the first commercial dengue vaccine.  Conclusions: We demonstrate that both genome assembly and detection of a low number of viral sequences are possible through the unbiased sequencing of clinical material. These methods may help ascertain causal agents for febrile illnesses with no known cause.


Sign in / Sign up

Export Citation Format

Share Document