Poliovirus vaccination: current understanding of poliovirus interactions in humans and implications for the eradication of poliomyelitis

1999 ◽  
Vol 1 (13) ◽  
pp. 1-17 ◽  
Author(s):  
Philip D. Minor
Keyword(s):  
Informed Choice ◽  
Oral Route ◽  
World Health ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Live Virus ◽  
Live Vaccines ◽  
The World ◽  
Strain Virus

Poliomyelitis is a paralytic disease of the motor neurones of the central nervous system, which is caused by poliovirus. The virus is transmitted by the faecal–oral route, and if virus replication is confined to the gut, it is harmless. Poliomyelitis is an ancient human disease, but was rare until the beginning of the 20th century, when children began to be exposed to the virus at older ages and were, therefore, no longer protected by maternal antibody, which had already been lost. Inactivated polio vaccines are increasingly being used in those countries in which poliomyelitis has been brought under control; however, live vaccines are still the most widely used types and the World Health Organization (WHO) have set the goal of using such vaccines to eliminate the wild-type virus throughout the world by the year 2000. Substantial progress has been made to this end; however, the strains of poliovirus that are used as vaccines are able to adapt rapidly to the human gut, losing their attenuated (weakened) character within a few weeks. Currently, there is urgent debate about the best method of stopping vaccination against poliomyelitis once the wild-type poliovirus has been eliminated completely, so that the vaccine-strain virus will also be eliminated. Proposed strategies include the abrupt cessation of vaccination with the live virus worldwide, followed by the optional use of inactivated vaccines for an appropriate period. Further information about both the epidemiology and the pathogenesis of the disease is required before an informed choice can be made. The topics covered in this article include a brief history of studies of the disease, its pathogenesis and its control by vaccination, the molecular biology of the live vaccines, which have been extremely successful in controlling poliomyelitis so far, and the concerns that are raised as the eradication of the wild-type virus approaches.

scholarly journals Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant

2021 ◽  
Author(s):  
Dong-Kyun Ryu ◽  
Rina Song ◽  
Minsoo Kim ◽  
Young-Il Kim ◽  
Cheolmin Kim ◽  
...  
Keyword(s):  
South African ◽  
Wild Type Virus ◽  
List Type ◽  
Type Virus ◽  
Wild Type ◽  
Therapeutic Dosage ◽  
Similar Extent ◽  
Live Virus

AbstractThe global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.HighlightsCT-P59 significantly inhibit B.1.1.7 variant to a similar extent as to wild type virusCT-P59 showed reduced potency against the B.1.351 variant in in vitro studiesTherapeutic dosage of CT-P59 showed in vivo neutralizing potency against B.1.351 in ferret challenge study.

scholarly journals The Disease Severity and Clinical Outcomes of the SARS-CoV-2 Variants of Concern

2021 ◽  
Vol 9 ◽  
Author(s):  
Lixin Lin ◽  
Ying Liu ◽  
Xiujuan Tang ◽  
Daihai He
Keyword(s):  
Random Effects ◽  
Meta Analysis ◽  
Hospitalization Rate ◽  
Wild Type Virus ◽  
Severe Illness ◽  
Type Virus ◽  
Wild Type ◽  
The World ◽  
Alpha Beta ◽  
Severity Of The Disease

With the continuation of the pandemic, many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have appeared around the world. Owing to a possible risk of increasing the transmissibility of the virus, severity of the infected individuals, and the ability to escape the antibody produced by the vaccines, the four SARS-CoV-2 variants of Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) have attracted the most widespread attention. At present, there is a unified conclusion that these four variants have increased the transmissibility of SARS-CoV-2, but the severity of the disease caused by them has not yet been determined. Studies from June 1, 2020 to October 15, 2021 were considered, and a meta-analysis was carried out to process the data. Alpha, Beta, Gamma, and Delta variants are all more serious than the wild-type virus in terms of hospitalization, ICU admission, and mortality, and the Beta and Delta variants have a higher risk than the Alpha and Gamma variants. Notably, the random effects of Beta variant to the wild-type virus with respect to hospitalization rate, severe illness rate, and mortality rate are 2.16 (95% CI: 1.19–3.14), 2.23 (95% CI: 1.31–3.15), and 1.50 (95% CI: 1.26–1.74), respectively, and the random effects of Delta variant to the wild-type virus are 2.08 (95% CI: 1.77–2.39), 3.35 (95% CI: 2.5–4.2), and 2.33 (95% CI: 1.45–3.21), respectively. Although, the emergence of vaccines may reduce the threat posed by SARS-CoV-2 variants, these are still very important, especially the Beta and Delta variants.

The URNA Genes of Herpesvirus Saimiri (Strain C488) Are Dispensable for Transformation of Human T Cells In Vitro

1999 ◽  
Vol 73 (12) ◽  
pp. 10551-10555 ◽  
Author(s):  
Armin Ensser ◽  
André Pfinder ◽  
Ingrid Müller-Fleckenstein ◽  
Bernhard Fleckenstein
Keyword(s):  
Cell Culture ◽  
Herpesvirus Saimiri ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Human T Cell ◽  
Human T Cells ◽  
Small Nuclear Rnas ◽  
T Cell Lines

ABSTRACT The herpesvirus saimiri strain C488 genome contains five genes for small nuclear RNAs, termed herpesvirus saimiri URNAs (or HSURs). Using a cosmid-based approach, all HSURs were precisely deleted from the genome. The mutant virus replicated at levels that were similar to those of wild-type viruses in OMK cells. Although the HSURs are expressed in wild-type virus-transformed human T-cell lines, the deletion does not affect viral transformation in cell culture.

scholarly journals Kinetics of Neutralizing Antibodies of COVID-19 Patients Tested Using Clinical D614G, B.1.1.7 and B 1.351 Isolates in Microneutralization Assays

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 996
Author(s):  
Jenni Virtanen ◽  
Ruut Uusitalo ◽  
Essi M. Korhonen ◽  
Kirsi Aaltonen ◽  
Teemu Smura ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Acute Infection ◽  
Clinical Isolates ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Kinetics Of

Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.

scholarly journals A Replication-Defective Gammaherpesvirus Efficiently Establishes Long-Term Latency in Macrophages but Not in B Cells In Vivo

2008 ◽  
Vol 82 (17) ◽  
pp. 8500-8508 ◽  
Author(s):  
Haiyan Li ◽  
Kazufumi Ikuta ◽  
John W. Sixbey ◽  
Scott A. Tibbetts
Keyword(s):  
B Cells ◽  
Viral Genome ◽  
Lytic Replication ◽  
Mutant Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Virus Latency

ABSTRACT Murine gammaherpesvirus 68 (γHV68 or MHV68) is genetically related to the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), providing a useful system for in vivo studies of the virus-host relationship. To begin to address fundamental questions about the mechanisms of the establishment of gammaherpesvirus latency, we previously generated a replication-defective γHV68 lacking the expression of the single-stranded DNA binding protein encoded by orf6. In work presented here, we demonstrate that this mutant virus established a long-term infection in vivo that was molecularly identical to wild-type virus latency. Thus, despite the absence of an acute phase of lytic replication, the mutant virus established a chronic infection in which the viral genome (i) was maintained as an episome and (ii) expressed latency-associated, but not lytic replication-associated, genes. Macrophages purified from mice infected with the replication-defective virus harbored viral genome at a frequency that was nearly identical to that of wild-type γHV68; however, the frequency of B cells harboring viral genome was greatly reduced in the absence of lytic replication. Thus, this replication-defective gammaherpesvirus efficiently established in vivo infection in macrophages that was molecularly indistinguishable from wild-type virus latency. These data point to a critical role for lytic replication or reactivation in the establishment or maintenance of latent infection in B cells.

scholarly journals Novel Single-Cell-Level Phenotypic Assay for Residual Drug Susceptibility and Reduced Replication Capacity of Drug-Resistant Human Immunodeficiency Virus Type 1

2004 ◽  
Vol 78 (4) ◽  
pp. 1718-1729 ◽  
Author(s):  
Haili Zhang ◽  
Yan Zhou ◽  
Cecily Alcock ◽  
Tara Kiefer ◽  
Daphne Monie ◽  
...  
Keyword(s):  
Drug Combination ◽  
Wild Type Virus ◽  
Replication Capacity ◽  
Drug Resistant ◽  
Type Virus ◽  
Wild Type ◽  
Cell Level ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-infected individuals who develop drug-resistant virus during antiretroviral therapy may derive benefit from continued treatment for two reasons. First, drug-resistant viruses can retain partial susceptibility to the drug combination. Second, therapy selects for drug-resistant viruses that may have reduced replication capacities relative to archived, drug-sensitive viruses. We developed a novel single-cell-level phenotypic assay that allows these two effects to be distinguished and compared quantitatively. Patient-derived gag-pol sequences were cloned into an HIV-1 reporter virus that expresses an endoplasmic reticulum-retained Env-green fluorescent protein fusion. Flow cytometric analysis of single-round infections allowed a quantitative analysis of viral replication over a 4-log dynamic range. The assay faithfully reproduced known in vivo drug interactions occurring at the level of target cells. Simultaneous analysis of single-round infections by wild-type and resistant viruses in the presence and absence of the relevant drug combination divided the benefit of continued nonsuppressive treatment into two additive components, residual virus susceptibility to the drug combination and selection for drug-resistant variants with diminished replication capacities. In some patients with drug resistance, the dominant circulating viruses retained significant susceptibility to the combination. However, in other cases, the dominant drug-resistant viruses showed no residual susceptibility to the combination but had a reduced replication capacity relative to the wild-type virus. In this case, simplification of the regimen might still allow adequate suppression of the wild-type virus. In a third pattern, the resistant viruses had no residual susceptibility to the relevant drug regimen but nevertheless had a replication capacity equivalent to that of wild-type virus. In such cases, there is no benefit to continued treatment. Thus, the ability to simultaneously analyze residual susceptibility and reduced replication capacity of drug-resistant viruses may provide a basis for rational therapeutic decisions in the setting of treatment failure.

scholarly journals Vaccinia Virus Envelope H3L Protein Binds to Cell Surface Heparan Sulfate and Is Important for Intracellular Mature Virion Morphogenesis and Virus Infection In Vitro and In Vivo

2000 ◽  
Vol 74 (7) ◽  
pp. 3353-3365 ◽  
Author(s):  
Chi-Long Lin ◽  
Che-Sheng Chung ◽  
Hans G. Heine ◽  
Wen Chang
Keyword(s):  
Cell Surface ◽  
Vaccinia Virus ◽  
Heparan Sulfate ◽  
Mutant Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Virion Morphogenesis

ABSTRACT An immunodominant antigen, p35, is expressed on the envelope of intracellular mature virions (IMV) of vaccinia virus. p35 is encoded by the viral late gene H3L, but its role in the virus life cycle is not known. This report demonstrates that soluble H3L protein binds to heparan sulfate on the cell surface and competes with the binding of vaccinia virus, indicating a role for H3L protein in IMV adsorption to mammalian cells. A mutant virus defective in expression of H3L (H3L−) was constructed; the mutant virus has a small plaque phenotype and 10-fold lower IMV and extracellular enveloped virion titers than the wild-type virus. Virion morphogenesis is severely blocked and intermediate viral structures such as viral factories and crescents accumulate in cells infected with the H3L− mutant virus. IMV from the H3L− mutant virus are somewhat altered and less infectious than wild-type virions. However, cells infected by the mutant virus form multinucleated syncytia after low pH treatment, suggesting that H3L protein is not required for cell fusion. Mice inoculated intranasally with wild-type virus show high mortality and severe weight loss, whereas mice infected with H3L− mutant virus survive and recover faster, indicating that inactivation of the H3L gene attenuates virus virulence in vivo. In summary, these data indicate that H3L protein mediates vaccinia virus adsorption to cell surface heparan sulfate and is important for vaccinia virus infection in vitro and in vivo. In addition, H3L protein plays a role in virion assembly.

Sign in / Sign up

Export Citation Format

Share Document