scholarly journals Characterization of linear epitope specificity of antibodies potentially contributing to spontaneous clearance of hepatitis C virus

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256816
Author(s):  
Asma Ahsan ◽  
Saira Dar ◽  
Fareeha Hassan ◽  
Farkhanda Ghafoor ◽  
Muhammad Haroon Yousuf ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Potential Role ◽  
Viral Clearance ◽  
Spontaneous Clearance ◽  
Linear Epitope ◽  
Specific Antibodies ◽  
Spontaneous Viral Clearance ◽  
Epitope Specificity ◽  
Linear Epitopes

Background Around 30% of the HCV infected patients can spontaneously clear the virus. Cumulative evidence suggests the role of neutralizing antibodies in such spontaneous resolution. Understanding the epitope specificity of such antibodies will inform the rational vaccine design as such information is limited to date. In addition to conformational epitope targeted antibodies, linear epitope specific antibodies have been identified that are broadly cross reactive against diverse HCV strains. In this study, we have characterized the potential role of three conserved linear epitopes in the spontaneous clearance of HCV. Methods We tested the reactivity of sera from chronic patients (CP) and spontaneous resolvers (SR) with linear peptides corresponding to three conserved regions of HCV envelope protein E2 spanning amino acids 412–423, 523–532 and 432–443 using ELISA. Subsequently, we characterized the dependency of HCV neutralization by the reactive serum samples on the antibodies specific for these epitopes using pseudoparticle-based neutralization assay. In ELISA most of the CP sera showed reactivity to multiple peptides while most of the SR samples were reactive to a single peptide suggesting presence of more specific antibodies in the SR sera. In most of the HCVpp neutralizing sera of particular peptide reactivity the neutralization was significantly affected by the presence of respective peptide. HCV neutralization by CP sera was affected by multiple peptides while 75% of the HCVpp neutralizing SR sera were competed by the 432 epitope. Conclusions These findings suggest that individuals who spontaneously resolve HCV infection at the acute phase, can produce antibodies specific for conserved linear epitopes, and those antibodies can potentially play a role in the spontaneous viral clearance. The epitope present in the 432–443 region of E2 was identified as the primary neutralizing epitope with potential role in spontaneous viral clearance and this epitope potentiates for the design of immunogen for prophylactic vaccine.

scholarly journals Host Immune Responses to Chronic Adenovirus Infections in Human and Nonhuman Primates

2008 ◽  
Vol 83 (6) ◽  
pp. 2623-2631 ◽  
Author(s):  
Roberto Calcedo ◽  
Luk H. Vandenberghe ◽  
Soumitra Roy ◽  
Suryanarayan Somanathan ◽  
Lili Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Peripheral Blood ◽  
Neutralizing Antibodies ◽  
Potential Role ◽  
Low Frequencies ◽  
Host Immune Responses ◽  
Virus Genomes ◽  
The Impact

ABSTRACT Recent studies indicate that great apes and macaques chronically shed adenoviruses in the stool. Shedding of adenovirus in the stool of humans is less prevalent, although virus genomes persist in gut-associated lymphoid tissue in the majority of individual samples. Chimpanzees have high levels of broadly reactive neutralizing antibodies to adenoviruses in serum, with very low frequencies of adenovirus-specific T cells in peripheral blood. A similar situation exists in macaques; sampling of guts from macaques demonstrated adenovirus-specific T cells in lamina propria. Humans show intermediate levels of serum neutralizing antibodies, with adenovirus-specific T cells in peripheral blood of all individuals sampled and about 20% of samples from the gut, suggesting a potential role of T cells in better controlling virus replication in the gut. The overall structure of the E3 locus, which is involved in modulating the host's response to infection, is degenerate in humans compared to that in apes, which may contribute to diminished evasion of host immunity. The impact of adenovirus persistence and immune responses should be considered when using adenoviral vectors in gene therapy and genetic vaccines.

scholarly journals Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Supaporn Wacharapluesadee ◽  
Chee Wah Tan ◽  
Patarapol Maneeorn ◽  
Prateep Duengkae ◽  
Feng Zhu ◽  
...  
Keyword(s):  
Southeast Asia ◽  
Neutralizing Antibodies ◽  
Potential Role ◽  
Cross Border ◽  
Southern Thailand ◽  
The Many ◽  
Border Surveillance ◽  
Bat Coronavirus ◽  
Japan And China

AbstractAmong the many questions unanswered for the COVID-19 pandemic are the origin of SARS-CoV-2 and the potential role of intermediate animal host(s) in the early animal-to-human transmission. The discovery of RaTG13 bat coronavirus in China suggested a high probability of a bat origin. Here we report molecular and serological evidence of SARS-CoV-2 related coronaviruses (SC2r-CoVs) actively circulating in bats in Southeast Asia. Whole genome sequences were obtained from five independent bats (Rhinolophus acuminatus) in a Thai cave yielding a single isolate (named RacCS203) which is most related to the RmYN02 isolate found in Rhinolophus malayanus in Yunnan, China. SARS-CoV-2 neutralizing antibodies were also detected in bats of the same colony and in a pangolin at a wildlife checkpoint in Southern Thailand. Antisera raised against the receptor binding domain (RBD) of RmYN02 was able to cross-neutralize SARS-CoV-2 despite the fact that the RBD of RacCS203 or RmYN02 failed to bind ACE2. Although the origin of the virus remains unresolved, our study extended the geographic distribution of genetically diverse SC2r-CoVs from Japan and China to Thailand over a 4800-km range. Cross-border surveillance is urgently needed to find the immediate progenitor virus of SARS-CoV-2.

scholarly journals α-Hemolysin-Aided Oligomerization of the Spike Protein RBD Resulted in Improved Immunogenicity and Neutralization Against SARS-CoV-2 Variants

2021 ◽  
Vol 12 ◽  
Author(s):  
Jintao Zou ◽  
Haiming Jing ◽  
Xiaoli Zhang ◽  
Yiheng Liu ◽  
Zhuo Zhao ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Neutralization Assay ◽  
Spike Protein ◽  
Wild Type Virus ◽  
Carrier Protein ◽  
Specific Antibodies ◽  
Linear Epitopes ◽  
Cellular Immune ◽  
Candidate Antigen

The increase in confirmed COVID-19 cases and SARS-CoV-2 variants calls for the development of safe and broad cross-protective vaccines. The RBD of the spike protein was considered to be a safe and effective candidate antigen. However, the low immunogenicity limited its application in vaccine development. Herein, we designed and obtained an RBD heptamer (mHla-RBD) based on a carrier protein-aided assembly strategy. The molecular weight of mHla-RBD is up to 450 kDa, approximately 10 times higher than that of the RBD monomer. When formulated with alum adjuvant, mHla-RBD immunization significantly increased the immunogenicity of RBD, as indicated by increased titers of RBD-specific antibodies, neutralizing antibodies, Th2 cellular immune response, and pseudovirus neutralization activity, when compared to RBD monomer. Furthermore, we confirmed that RBD-specific antibodies predominantly target conformational epitopes, which was approximately 200 times that targeting linear epitopes. Finally, a pseudovirus neutralization assay revealed that neutralizing antibodies induced by mHla-RBD against different SARS-CoV-2 variants were comparable to those against the wild-type virus and showed broad-spectrum neutralizing activity toward different SARS-CoV-2 variants. Our results demonstrated that mHla-RBD is a promising candidate antigen for development of SARS-CoV-2 vaccines and the mHla could serve as a universal carrier protein for antigen design.

scholarly journals Sialoadhesin and CD163 join forces during entry of the porcine reproductive and respiratory syndrome virus

2008 ◽  
Vol 89 (12) ◽  
pp. 2943-2953 ◽  
Author(s):  
Hanne Van Gorp ◽  
Wander Van Breedam ◽  
Peter L. Delputte ◽  
Hans J. Nauwynck
Keyword(s):  
Potential Role ◽  
Heparan Sulphate ◽  
Virus Production ◽  
Productive Infection ◽  
Respiratory Syndrome Virus ◽  
Specific Antibodies ◽  
Virus Uncoating

The porcine reproductive and respiratory syndrome virus (PRRSV) shows a restricted tropism for subsets of porcine macrophages in vivo. To date, two PRRSV receptors have been identified on primary macrophages, heparan sulphate for binding and sialoadhesin for binding and internalization. However, additional factors are needed because the expression of both receptors in non-permissive cells results in virus internalization but not in virus uncoating and productive infection. Recently, CD163 was described as a PRRSV receptor on Marc-145 cells that renders non-permissive cells susceptible to PRRSV. Therefore, the potential role of CD163 in PRRSV entry in macrophages and its potential interplay with sialoadhesin were studied. Incubation of macrophages at 37 °C with either sialoadhesin- or CD163-specific antibodies reduced PRRSV infection by up to 75 %, while infection was completely blocked by a combination of both antibodies. When incubated at 4 °C, only sialoadhesin- and not CD163-specific antibodies reduced PRRSV infection. In addition, confocal analysis of PRRSV entry in non-permissive cells expressing only sialoadhesin showed PRRSV internalization but no uncoating. In contrast, when both sialoadhesin and CD163 were expressed, PRRSV was uncoated upon internalization, resulting in productive infection. Virus internalization was not observed when only CD163 was expressed; although, cells became productively infected. Thus, sialoadhesin is confirmed as a PRRSV internalization receptor and CD163 is shown to be involved in PRRSV entry, probably during uncoating. Co-expression of recombinant sialoadhesin and CD163 in non-permissive cells increased virus production 10–100 times compared with cells expressing only CD163, sustaining the requirement of both for efficient PRRSV infection.

scholarly journals Potential Role of Specific Antibodies as Important Vaccine Induced Protective Mechanism against Aeromonas salmonicida in Rainbow Trout

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46733 ◽  
Author(s):  
Kasper Rømer Villumsen ◽  
Inger Dalsgaard ◽  
Lars Holten-Andersen ◽  
Martin Kristian Raida
Keyword(s):  
Rainbow Trout ◽  
Potential Role ◽  
Aeromonas Salmonicida ◽  
Protective Mechanism ◽  
Specific Antibodies

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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