scholarly journals Persistent SARS-CoV-2 infection and increasing viral variants in children and young adults with impaired humoral immunity

2021 ◽  
Author(s):  
Thao T. Truong ◽  
Alex Ryutov ◽  
Utsav Pandey ◽  
Rebecca Yee ◽  
Lior Goldberg ◽  
...  
Keyword(s):  
Los Angeles ◽  
Immune Responses ◽  
Immune Escape ◽  
Lymphoblastic Leukemia ◽  
Viral Evolution ◽  
Host Immune Responses ◽  
Pediatric Hematology ◽  
Viral Culture ◽  
Routine Surveillance ◽  
Serological Studies

SummaryBackgroundThere is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses.MethodsWe describe three patients with acute lymphoblastic leukemia who were persistently positive for SARS-CoV-2 by real-time polymerase chain reaction. Viral viability from longitudinally-collected specimens was assessed. Whole-genome sequencing and serological studies were performed to measure viral evolution and evidence of immune escape.FindingsWe found compelling evidence of ongoing replication and infectivity for up to 162 days from initial positive by subgenomic RNA, single-stranded RNA, and viral culture analysis. Our results reveal a broad spectrum of infectivity, host immune responses, and accumulation of mutations, some with the potential for immune escape.InterpretationOur results highlight the need to reassess infection control precautions in the management and care of immunocompromised patients. Routine surveillance of mutations and evaluation of their potential impact on viral transmission and immune escape should be considered.FundingThe work was partially funded by The Saban Research Institute at Children’s Hospital Los Angeles intramural support for COVID-19 Directed Research (X.G. and J.D.B.), the Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHSN272201400007C (A.P.), NIH/NIAID R01AI127877 (S.D.B.), NIH/NIAID R01AI130398 (S.D.B.), NIH 1U54CA260517 (S.D.B.), an endowment to S.D.B. from the Crown Family Foundation, an Early Postdoc.Mobility Fellowship Stipend to O.F.W. from the Swiss National Science Foundation (SNSF), and a Coulter COVID-19 Rapid Response Award to S.D.B. L.G. is a SHARE Research Fellow in Pediatric Hematology-Oncology.

scholarly journals Porcine Reproductive and Respiratory Syndrome Virus: Immune Escape and Application of Reverse Genetics in Attenuated Live Vaccine Development

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 480
Author(s):  
Honglei Wang ◽  
Yangyang Xu ◽  
Wenhai Feng
Keyword(s):  
Immune Responses ◽  
Reverse Genetics ◽  
Vaccine Development ◽  
Immune Escape ◽  
Rna Virus ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Live Vaccines ◽  
Host Immune Responses ◽  
Inactivated Vaccines

Porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus widely prevalent in pigs, results in significant economic losses worldwide. PRRSV can escape from the host immune response in several processes. Vaccines, including modified live vaccines and inactivated vaccines, are the best available countermeasures against PRRSV infection. However, challenges still exist as the vaccines are not able to induce broad protection. The reason lies in several facts, mainly the variability of PRRSV and the complexity of the interaction between PRRSV and host immune responses, and overcoming these obstacles will require more exploration. Many novel strategies have been proposed to construct more effective vaccines against this evolving and smart virus. In this review, we will describe the mechanisms of how PRRSV induces weak and delayed immune responses, the current vaccines of PRRSV, and the strategies to develop modified live vaccines using reverse genetics systems.

scholarly journals Antibiotics in early life and childhood pre-B-ALL. Reasons to analyze a possible new piece in the puzzle

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
T. M. Cardesa-Salzmann ◽  
A. Simon ◽  
N. Graf
Keyword(s):  
Immune Responses ◽  
Early Life ◽  
Lymphoblastic Leukemia ◽  
Antibiotic Use ◽  
Intestinal Microbiome ◽  
Microbial Composition ◽  
Hematopoietic Stem ◽  
Childhood All ◽  
Host Immune Responses

AbstractAcute lymphoblastic leukemia (ALL) is the most common pediatric cancer with precursor B-cell ALL (pB-ALL) accounting for ~ 85% of the cases. Childhood pB-ALL development is influenced by genetic susceptibility and host immune responses. The role of the intestinal microbiome in leukemogenesis is gaining increasing attention since Vicente-Dueñas’ seminal work demonstrated that the gut microbiome is distinct in mice genetically predisposed to ALL and that the alteration of this microbiome by antibiotics is able to trigger pB-ALL in Pax5 heterozygous mice in the absence of infectious stimuli. In this review we provide an overview on novel insights on the role of the microbiome in normal and preleukemic hematopoiesis, inflammation, the effect of dysbiosis on hematopoietic stem cells and the emerging importance of the innate immune responses in the conversion from preleukemic to leukemic state in childhood ALL. Since antibiotics, which represent one of the most widely used medical interventions, alter the gut microbial composition and can cause a state of dysbiosis, this raises exciting epidemiological questions regarding the implications for antibiotic use in early life, especially in infants with a a preleukemic “first hit”. Sheading light through a rigorous study on this piece of the puzzle may have broad implications for clinical practice.

scholarly journals Genetically barcoded SIV reveals the emergence of escape mutations in multiple viral lineages during immune escape

2019 ◽  
Vol 117 (1) ◽  
pp. 494-502
Author(s):  
Taina T. Immonen ◽  
Celine Camus ◽  
Carolyn Reid ◽  
Christine M. Fennessey ◽  
Gregory Q. Del Prete ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Escape ◽  
Rhesus Macaques ◽  
Quantitative Measure ◽  
Population Level ◽  
Therapeutic Interventions ◽  
Viral Escape ◽  
Virus Population ◽  
Host Immune Responses ◽  
Immune Pressure

The rapidity of replication coupled with a high mutation rate enables HIV to evade selective pressures imposed by host immune responses. Investigating the ability of HIV to escape different selection forces has generally relied on population-level measures, such as the time to detectable escape mutations in plasma and the rate these mutations subsequently take over the virus population. Here we employed a barcoded synthetic swarm of simian immunodeficiency virus (SIV) in rhesus macaques to investigate the generation and selection of escape mutations within individual viral lineages at the Mamu-A*01-restricted Tat-SL8 epitope. We observed the persistence of more than 1,000 different barcode lineages following selection after acquiring escape mutations. Furthermore, the increased resolution into the virus population afforded by barcode analysis revealed changes in the population structure of the viral quasispecies as it adapted to immune pressure. The high frequency of emergence of escape mutations in parallel viral lineages at the Tat-SL8 epitope highlights the challenge posed by viral escape for the development of T cell-based vaccines. Importantly, the level of viral replication required for generating escape mutations in individual lineages can be directly estimated using the barcoded virus, thereby identifying the level of efficacy required for a successful vaccine to limit escape. Overall, assessing the survival of barcoded viral lineages during selection provides a direct and quantitative measure of the stringency of the underlying genetic bottleneck, making it possible to predict the ability of the virus to escape selective forces induced by host immune responses as well as during therapeutic interventions.

scholarly journals Molecular Mechanisms of Immune Escape for Foot-and-Mouth Disease Virus

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 729
Author(s):  
Bo Yang ◽  
Xiaohui Zhang ◽  
Dajun Zhang ◽  
Jing Hou ◽  
GuoWei Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Virus ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Immune Responses ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Vesicular Disease

Foot-and-mouth disease virus (FMDV) causes a highly contagious vesicular disease in cloven-hoofed livestock that results in severe consequences for international trade, posing a great economic threat to agriculture. The FMDV infection antagonizes the host immune responses via different signaling pathways to achieve immune escape. Strategies to escape the cell immune system are key to effective infection and pathogenesis. This review is focused on summarizing the recent advances to understand how the proteins encoded by FMDV antagonize the host innate and adaptive immune responses.

scholarly journals Glycosylation at Asn91 of H1N1 haemagglutinin affects binding to glycan receptors

2012 ◽  
Vol 444 (3) ◽  
pp. 429-435 ◽  
Author(s):  
Akila Jayaraman ◽  
Xiaoying Koh ◽  
Jing Li ◽  
Rahul Raman ◽  
Karthik Viswanathan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Viral Evolution ◽  
Glycosylation Site ◽  
Host Immune Responses ◽  
Glycosylation Sites ◽  
Host Cell Surface ◽  
Glycan Receptors ◽  
Receptor Binding Specificity ◽  
Viral Surface

The glycoprotein HA (haemagglutinin) on the surface of influenza A virus plays a central role in recognition and binding to specific host cell-surface glycan receptors and in fusion of viral membrane to the host nuclear membrane during viral replication. Given the abundance of HA on the viral surface, this protein is also the primary target for host innate and adaptive immune responses. Although addition of glycosylation sites on HA are a part of viral evolution to evade the host immune responses, there are specific glycosylation sites that are conserved during most of the evolution of the virus. In the present study, it was demonstrated that one such conserved glycosylation site at Asn91 in H1N1 HA critically governs the glycan receptor-binding specificity and hence would potentially impinge on the host adaptation of the virus.

scholarly journals Emerging role and therapeutic application of exosome in hepatitis virus infection and associated diseases

2021 ◽  
Author(s):  
Ying Shi ◽  
Lingyao Du ◽  
Duoduo Lv ◽  
Yan Li ◽  
Zilong Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cell ◽  
Immune Escape ◽  
Hepatitis Virus ◽  
Immune Defense ◽  
Therapeutic Application ◽  
Hepatitis Viruses ◽  
Virus Eradication ◽  
Host Immune Responses ◽  
Protein Components

AbstractHepatitis viruses are chief pathogens of hepatitis and end-stage liver diseases. Their replication and related pathogenic process highly rely on the host micro-environment and multiple cellular elements, including exosomes. Representing with a sort of cell-derived vesicle structure, exosomes were considered to be dispensable cellular components, even wastes. Along with advancing investigation, a specific profile of exosome in driving hepatitis viruses’ infection and hepatic disease progression is revealed. Exosomes greatly affect the pathogenesis of hepatitis viruses by mediating their replication and modulating the host immune responses. The characteristics of host exosomes are markedly changed after infection with hepatitis viruses. Exosomes released from hepatitis virus-infected cells can carry viral nucleic or protein components, thereby acting as an effective subterfuge for hepatitis viruses by participating in viral transportation and immune escape. On the contrary, immune cell-derived exosomes contribute toward the innate antiviral immune defense and virus eradication. There is growing evidence supporting the application of exosomal biomarkers for predicting disease progress or therapeutic outcome, while exosomal nanoshuttles are regarded as promising therapeutic options based on their delivery properties and immune compatibility. In this review, we summarize the biogenesis and secretion mechanism of exosomes, review the recent findings pertaining to the role of exosomes in the interplay between hepatitis viruses and innate immune responses, and conclude their potential in further therapeutic application.

scholarly journals Genomic Evidence of a Sars-Cov-2 Reinfection Case With E484K Spike Mutation in Brazil

2021 ◽  
Author(s):  
Carolina Kymie Vasques Nonaka ◽  
Marília Miranda Franco ◽  
Tiago Gräf ◽  
Ana Verena Almeida Mendes ◽  
Renato Santana de Aguiar ◽  
...  
Keyword(s):  
South Africa ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Viral Evolution ◽  
First Episode ◽  
Receptor Binding Domain ◽  
First Case ◽  
Potential Impact ◽  
The Uk

To date, uncertainty remains about how long the protective immune responses against SARS-CoV-2 persists and the first reports of suspected reinfection began to be described in recovered patients months after the first episode. Viral evolution may favor reinfections, and the recently described spike mutations, particularly in the receptor binding domain (RBD) in SARS-CoV-2 lineages circulating in the UK, South Africa, and most recently in Brazil, have raised concern on their potential impact in infectivity and immune escape. We report the first case of reinfection from genetically distinct SARS-CoV-2 lineage presenting the E484K spike mutation in Brazil, a variant associated with escape from neutralizing antibodies.

Role of convalescent plasma therapy in new Coronavirus disease (nCOVID-19): A review

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 546-549
Author(s):  
Shweta Dadarao Parwe ◽  
Milind Abhimanyu Nisargandha ◽  
Rishikesh Thakre
Keyword(s):  
Clinical Trial ◽  
Immune Responses ◽  
Indian Population ◽  
Preventive Treatment ◽  
The Body ◽  
Therapeutic Antibodies ◽  
Plasma Therapy ◽  
Host Immune Responses ◽  
Transparent Liquid

Hitherto, there is no proper line of treatment for the new (nCOVID19). The development of unique antiviral drugs has taken precedence. Therapeutic antibodies () will be a significantly beneficial agent against nCOVID-19. Here the host immune responses to new discussed in this review provide strategy and further treatment and understanding of clinical interventions against nCOVID-19. Plasma therapy uses the antibodies found in the blood of people recovering (or convalesced) from an infection to treat infected patients. When an infection occurs, the body begins producing proteins specially made to kill the germ, called antibodies. Those antibodies coat specifically plasma in the blood of survivors, the yellow transparent liquid blood portion for months or even years. research assesses plasma use from Convalescent patients of infected with nCOVID-19 as a possible preventive treatment. But it is not yet recommended as a line of treatment, and it is used as a clinical trial in the new in Indian population.

Sign in / Sign up

Export Citation Format

Share Document