698 NUCLEOS(T)IDE ANALOGUE TREATMENT FOR HBV INFECTIONS CAN RESULT IN THE SELECTION OF POSSIBLE HBV VACCINE ESCAPE MUTANTS

2008 ◽  
Vol 48 ◽  
pp. S260
Author(s):  
L. Yuen ◽  
P. Revill ◽  
V. Soriano ◽  
J. Sheldon ◽  
S. Locarnini
Keyword(s):  
Hbv Vaccine ◽  
Escape Mutants ◽  
Selection Of

scholarly journals Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection

2011 ◽  
Vol 7 (2) ◽  
pp. e1001273 ◽  
Author(s):  
Guido Ferrari ◽  
Bette Korber ◽  
Nilu Goonetilleke ◽  
Michael K. P. Liu ◽  
Emma L. Turnbull ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Functional Profile ◽  
Escape Mutants ◽  
Acute Hiv ◽  
Hiv 1 ◽  
Selection Of

scholarly journals A Quinolinone Compound Inhibiting the Oligomerization of Nucleoprotein of Influenza A Virus Prevents the Selection of Escape Mutants

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 337
Author(s):  
Juliann Nzembi Makau ◽  
Ken Watanabe ◽  
Hiroki Otaki ◽  
Satoshi Mizuta ◽  
Takeshi Ishikawa ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Nuclear Export ◽  
Influenza A ◽  
Drug Resistant ◽  
In Silico Screening ◽  
Antiviral Compound ◽  
Escape Mutants ◽  
2009 H1n1 ◽  
Emergence Of Resistance ◽  
Selection Of

The emergence of resistance to currently available anti-influenza drugs has heightened the need for antivirals with novel mechanisms of action. The influenza A virus (IAV) nucleoprotein (NP) is highly conserved and essential for the formation of viral ribonucleoprotein (vRNP), which serves as the template for replication and transcription. Recently, using in silico screening, we identified an antiviral compound designated NUD-1 (a 4-hydroxyquinolinone derivative) as a potential inhibitor of NP. In this study, we further analyzed the interaction between NUD-1 and NP and found that the compound interferes with the oligomerization of NP, which is required for vRNP formation, leading to the suppression of viral transcription, protein synthesis, and nuclear export of NP. We further assessed the selection of resistant variants by serially passaging a clinical isolate of the 2009 H1N1 pandemic influenza virus in the presence of NUD-1 or oseltamivir. NUD-1 did not select for resistant variants after nine passages, whereas oseltamivir selected for resistant variants after five passages. Our data demonstrate that NUD-1 interferes with the oligomerization of NP and less likely induces drug-resistant variants than oseltamivir; hence, it is a potential lead compound for the development of novel anti-influenza drugs.

scholarly journals Monoclonal Antibodies That Distinguish Antigenic Variants of Canine Parvovirus

2003 ◽  
Vol 10 (6) ◽  
pp. 1085-1089 ◽  
Author(s):  
Masato Nakamura ◽  
Kazuya Nakamura ◽  
Takayuki Miyazawa ◽  
Yukinobu Tohya ◽  
Masami Mochizuki ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Antigenic Site ◽  
Canine Parvovirus ◽  
The Other ◽  
Escape Mutants ◽  
Feline Parvovirus ◽  
Resistant Mutants ◽  
Selection Of

ABSTRACT Canine parvovirus (CPV) is classified as a member of the feline parvovirus (FPV) subgroup. CPV isolates are divided into three antigenic types: CPV type 2 (CPV-2), CPV-2a, and CPV-2b. Recently, new antigenic types of CPV were isolated from Vietnamese leopard cats and designated CPV-2c(a) or CPV-2c(b). CPV-2c viruses were distinguished from the other antigenic types of the FPV subgroup by the absence of reactivity with several monoclonal antibodies (MAbs). To characterize the antigenicity of CPV-2c, a panel of MAbs against CPV-2c was generated and epitopes recognized by these MAbs were examined by selection of escape mutants. Four MAbs were established and classified into three groups on the basis of their reactivities: MAbs which recognize CPV-2a, CPV-2b, and CPV-2c (MAbs 2G5 and 20G4); an MAb which reacts with only CPV-2b and CPV-2c(b) (MAb 21C3); and an MAb which recognizes all types of the FPV subgroup viruses (MAb 19D7). The reactivity of MAb 20G4 with CPV-2c was higher than its reactivities with CPV-2a and CPV-2b. These types of specificities of MAbs have not been reported previously. A mapping study by analysis of neutralization-resistant mutants showed that epitopes recognized by MAbs 21C3 and 19D7 belonged to antigenic site A. Substitution of the residues in site B and the other antigenic site influenced the epitope recognized by MAb 2G5. It was suggested that the epitope recognized by MAb 20G4 was related to antigenic site B. These MAbs are expected to be useful for the detection and classification of FPV subgroup isolates.

scholarly journals Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

2021 ◽  
Author(s):  
Elaine C. Chen ◽  
Pavlo Gilchuk ◽  
Seth J. Zost ◽  
Naveenchandra Suryadevara ◽  
Emma S. Winkler ◽  
...  
Keyword(s):  
Antibody Responses ◽  
Viral Escape ◽  
Spike Protein ◽  
Heptad Repeat ◽  
Healthy Individuals ◽  
Large Numbers ◽  
Escape Mutants ◽  
Insight Into ◽  
Selection Of

Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of SARS-CoV-2 infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identified 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, ACE2-blocking clone that protects in vivo), and others recognizing non-RBD epitopes that bound the heptad repeat 1 region of the S2 domain. Germline-revertant forms of some public clonotypes bound efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.

scholarly journals Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants

2001 ◽  
Vol 82 (2) ◽  
pp. 367-371 ◽  
Author(s):  
Patrick Soussan ◽  
Stanislas Pol ◽  
Florianne Garreau ◽  
Christian Bréchot ◽  
Dina Kremsdorf
Keyword(s):  
Chronic Hepatitis ◽  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Before And After ◽  
Escape Mutants ◽  
Selection Of

PreS2/S vaccination of chronic hepatitis B virus (HBV) carriers led to a reduction in HBV replication or clearance of virus in 30% of treated patients. This study assessed whether vaccinotherapy of chronic HBV carriers induced the selection of escape mutants in the envelope ‘a’ determinant and whether envelope genetic variability might affect the response to vaccination. No amino acid differences were observed in the ‘a’ determinant between sequences obtained before and after treatment (five responders and seven non-responders). However, alignment with HBV prototype sequences revealed seven amino acid changes. Two mutations (T140S and P127L) diverged from subtype variations. In the complete envelope sequence (five non-responders and five responders), ten amino acid modifications were detected between sequences obtained before and after treatment. The absence of any common mutations did not enable the definition of a hot spot of mutations implicated in the response to vaccination. Moreover, vaccinotherapy does not induce the selection of escape mutants in the ‘a’ determinant.

Specific properties of shRNA-mediated CCR5 downregulation that enhance the inhibition of HIV-1 infection in combination with shRNA targeting HIV-1 rev

2021 ◽  
Author(s):  
Maria E Cardona ◽  
Jorma Hinkula ◽  
Kristin Gustafsson ◽  
Birger Christensson ◽  
Britta Wahren ◽  
...  
Keyword(s):  
Infected Individual ◽  
Antiviral Effect ◽  
Endogenous Virus ◽  
Ccr5 Expression ◽  
Hairpin Rna ◽  
Escape Mutants ◽  
Human Ccr5 ◽  
Hiv 1 ◽  
Selection Of ◽  
Better Than

Abstract Treatment with RNAi against HIV-1 transcripts efficiently inhibits viral replication but induces selection of escape mutants; therefore, the CCR5 coreceptor was suggested as an additional target. Blocking viral and host transcripts improved the antiviral effect. We have used short hairpin RNA (shRNA) targeting the human CCR5 (shCCR5) or the HIV-1 rev (shRev) transcripts to demonstrate distinctive properties of anti-CCR5 shRNA: shCCR5 induced more sustained protection than shRev; partial reduction in CCR5 expression substantially decreased HIV-1 infection, and shCCR5 performed better than shRev in the mixed shRNA-treated and untreated cultures. These observations indicate that CCR5 inhibitors should be conveniently included in HIV-1 gene silencing treatment schedules when only a certain cell fraction is protected to further reduce endogenous virus in a properly ART-treated HIV-1 infected individual.

scholarly journals Selection of neutralizing antibody escape mutants with type A influenza virus HA-specific polyclonal antisera: possible significance for antigenic drift

1997 ◽  
Vol 118 (2) ◽  
pp. 149-154 ◽  
Author(s):  
S. M. CLEVELAND ◽  
H. P. TAYLOR ◽  
N. J. DIMMOCK
Keyword(s):  
Haemagglutination Inhibition ◽  
Antigenic Site ◽  
Neutralizing Antibody ◽  
Type A ◽  
Antigenic Drift ◽  
Progeny Virus ◽  
Escape Mutant ◽  
Virus Growth ◽  
Escape Mutants ◽  
Selection Of

Ten antisera were produced in rabbits by two or three intravenous injections of inactivated whole influenza type A virions. All contained haemagglutination-inhibition (HI) antibody directed predominantly to an epitope in antigenic site B and, in addition, various amounts of antibodies to an epitope in site A and in site D. The ability of untreated antisera to select neutralization escape mutants was investigated by incubating virus possessing the homologous haemagglutinin with antiserum adjusted to contain anti-B epitope HI titres of 100, 1000 and 10000 HIU/ml. Virus-antiserum mixtures were inoculated into embryonated hen's eggs, and progeny virus examined without further selection. Forty percent of the antisera at a titre of 1000 HIU/ml selected neutralizing antibody escape mutants as defined by their lack of reactivity to Mab HC10 (site B), and unchanged reactivity to other Mabs to site A and site D epitopes. All escape mutant-selecting antisera had a ratio of anti-site B (HC10)-epitope antibody[ratio ]other antibodies of [ges ]2·0[ratio ]1. The antiserum with the highest ratio (7·4[ratio ]1) selected escape mutants in all eggs tested in four different experiments. No antiserum used at a titre of 10000 HIU/ml allowed multiplication of any virus. All antisera used at a titre of 100 HIU/ml permitted virus growth, but this was wild-type (wt) virus. We conclude that a predominant epitope-specific antibody response, a titre of [ges ]1000 HIU/ml, and a low absolute titre of other antibodies ([les ]500 HIU/ml) are three requirements for the selection of escape mutants. None of the antisera in this study could have selected escape mutants without an appropriate dilution factor, so the occurrence of an escape mutant-selecting antiserum in nature is likely to be a rare event.

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