scholarly journals Experimental Infection of Adapted Influenza B Virus in Mice Model

2020 ◽  
Author(s):  
Elena Prokopyeva ◽  
Olga Kurskaya ◽  
Ivan Sobolev ◽  
Mariia Solomatina ◽  
Tatyana Murashkina ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Electron Microscopic Examination ◽  
Influenza B Virus ◽  
Influenza B ◽  
Post Inoculation ◽  
Mice Model ◽  
Electron Microscopic ◽  
B Virus

Over the years influenza B virus (IBV) contribute annual disease and can lead to serious respiratory disease among humans. More attention should be paid to the mammalian adaptive processes of B viruses and development of vaccines against current influenza. Because of preclinical trials of anti-influenza drugs are conducted mainly on mice, we developed adequate animal model using antigenically-relevant IBV strain for testing anti-influenza drugs and protective efficacy of flu vaccines. We serially passaged Victoria lineage (clade 1A) IBV 17 times in BALB/c mice. The adaptive amino acid substitutions were found in HA (T214I) and NA (D432N). By the electron microscopic examination, we showed spherical and elliptical shapes of IBV. Light microscopy showed that mouse-adapted B virus caused influenza pneumonia on day 6 post inoculation. We evaluated the illness pathogenicity, viral load and histopathological features of mouse-adapted IBV and estimated anti-influenza drugs and vaccine efficiency in vitro and in vivo. Assessment of investigational anti-influenza drug oseltamivir ethoxisuccinate and flu vaccine Ultrix® revealed effectivity against our mouse-adapted influenza B virus.

scholarly journals Experimental Infection Using Mouse-Adapted Influenza B Virus in a Mouse Model

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 470 ◽  
Author(s):  
Elena Prokopyeva ◽  
Olga Kurskaya ◽  
Ivan Sobolev ◽  
Mariia Solomatina ◽  
Tatyana Murashkina ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Drug Testing ◽  
Protective Efficacy ◽  
Influenza B Virus ◽  
Infection Model ◽  
Influenza B ◽  
Post Inoculation ◽  
B Virus

Every year, influenza B viruses (IBVs) contribute to annual illness, and infection can lead to serious respiratory disease among humans. More attention is needed in several areas, such as increasing virulence or pathogenicity of circulating B viruses and developing vaccines against current influenza. Since preclinical trials of anti-influenza drugs are mainly conducted in mice, we developed an appropriate infection model, using an antigenically-relevant IBV strain, for furtherance of anti-influenza drug testing and influenza vaccine protective efficacy analysis. A Victoria lineage (clade 1A) IBV was serially passaged 17 times in BALB/c mice, and adaptive amino acid substitutions were found in hemagglutinin (HA) (T214I) and neuraminidase (NA) (D432N). By electron microscopy, spherical and elliptical IBV forms were noted. Light microscopy showed that mouse-adapted IBVs caused influenza pneumonia on day 6 post inoculation. We evaluated the illness pathogenicity, viral load, and histopathological features of mouse-adapted IBVs and estimated anti-influenza drugs and vaccine efficiency in vitro and in vivo. Assessment of an investigational anti-influenza drug (oseltamivir ethoxysuccinate) and an influenza vaccine (Ultrix®, SPBNIIVS, Saint Petersburg, Russia) showed effectiveness against the mouse-adapted influenza B virus.

scholarly journals Influenza B Virus NS1-Truncated Mutants: Live-Attenuated Vaccine Approach

2008 ◽  
Vol 82 (21) ◽  
pp. 10580-10590 ◽  
Author(s):  
Rong Hai ◽  
Luis Martínez-Sobrido ◽  
Kathryn A. Fraser ◽  
Juan Ayllon ◽  
Adolfo García-Sastre ◽  
...  
Keyword(s):  
Reverse Genetics ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Type I ◽  
Live Attenuated Vaccine ◽  
Live Virus ◽  
B Virus

ABSTRACT Type B influenza viruses can cause substantial morbidity and mortality in the population, and vaccination remains by far the best means of protection against infections with these viruses. Here, we report the construction of mutant influenza B viruses for potential use as improved live-virus vaccine candidates. Employing reverse genetics, we altered the NS1 gene, which encodes a type I interferon (IFN) antagonist. The resulting NS1 mutant viruses induced IFN and, as a consequence, were found to be attenuated in vitro and in vivo. The absence of pathogenicity of the NS1 mutants in both BALB/c and C57BL/6 PKR−/− mice was confirmed. We also provide evidence that influenza B virus NS1 mutants induce a self-adjuvanted immune response and confer effective protection against challenge with both homologous and heterologous B virus strains in mice.

scholarly journals FluB-RAM and FluB-RANS: Genome Rearrangement as Safe and Efficacious Live Attenuated Influenza B Virus Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 897
Author(s):  
Stivalis Cardenas-Garcia ◽  
C. Joaquín Cáceres ◽  
Aarti Jain ◽  
Ginger Geiger ◽  
Jong-Suk Mo ◽  
...  
Keyword(s):  
Genome Rearrangement ◽  
Natural Infection ◽  
The Elderly ◽  
Respiratory Pathogen ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Cellular Immune

Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated influenza virus vaccines (LAIVs) are thought to induce both humoral and cellular immune responses by mimicking a natural infection, but their effectiveness has recently come into question. Thus, the opportunity exists to find alternative approaches to improve overall influenza vaccine effectiveness. Two alternative IBV backbones were developed with rearranged genomes, rearranged M (FluB-RAM) and a rearranged NS (FluB-RANS). Both rearranged viruses showed temperature sensitivity in vitro compared with the WT type B/Bris strain, were genetically stable over multiple passages in embryonated chicken eggs and were attenuated in vivo in mice. In a prime-boost regime in naïve mice, both rearranged viruses induced antibodies against HA with hemagglutination inhibition titers considered of protective value. In addition, antibodies against NA and NP were readily detected with potential protective value. Upon lethal IBV challenge, mice previously vaccinated with either FluB-RAM or FluB-RANS were completely protected against clinical disease and mortality. In conclusion, genome re-arrangement renders efficacious LAIV candidates to protect mice against IBV.

scholarly journals The NB Protein of Influenza B Virus Is Not Necessary for Virus Replication In Vitro

2003 ◽  
Vol 77 (10) ◽  
pp. 6050-6054 ◽  
Author(s):  
Masato Hatta ◽  
Yoshihiro Kawaoka
Keyword(s):  
Cell Culture ◽  
Virus Replication ◽  
Wild Type Virus ◽  
Influenza B Virus ◽  
Influenza B ◽  
Type Virus ◽  
Wild Type ◽  
B Virus

ABSTRACT The NB protein of influenza B virus is thought to function as an ion channel and therefore would be expected to have an essential function in viral replication. Because direct evidence for its absolute requirement in the viral life cycle is lacking, we generated NB knockout viruses by reverse genetics and tested their growth properties both in vitro and in vivo. Mutants not expressing NB replicated as efficiently as the wild-type virus in cell culture, whereas in mice they showed restricted growth compared with findings for the wild-type virus. Thus, the NB protein is not essential for influenza B virus replication in cell culture but promotes efficient growth in mice.

scholarly journals Development of an Alternative Modified Live Influenza B Virus Vaccine

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Jefferson J. S. Santos ◽  
Courtney Finch ◽  
Troy Sutton ◽  
Adebimpe Obadan ◽  
Isabel Aguirre ◽  
...  
Keyword(s):  
Influenza A ◽  
The United States ◽  
Influenza B Virus ◽  
Influenza B ◽  
Temperature Sensitive ◽  
Complete Protection ◽  
C Terminus ◽  
B Virus

ABSTRACT Influenza B virus (IBV) is considered a major human pathogen, responsible for seasonal epidemics of acute respiratory illness. Two antigenically distinct IBV hemagglutinin (HA) lineages cocirculate worldwide with little cross-reactivity. Live attenuated influenza virus (LAIV) vaccines have been shown to provide better cross-protective immune responses than inactivated vaccines by eliciting local mucosal immunity and systemic B cell- and T cell-mediated memory responses. We have shown previously that incorporation of temperature-sensitive (ts) mutations into the PB1 and PB2 subunits along with a modified HA epitope tag in the C terminus of PB1 resulted in influenza A viruses (IAV) that are safe and effective as modified live attenuated (att) virus vaccines (IAV att). We explored whether analogous mutations in the IBV polymerase subunits would result in a stable virus with an att phenotype. The PB1 subunit of the influenza B/Brisbane/60/2008 strain was used to incorporate ts mutations and a C-terminal HA tag. Such modifications resulted in a B/Bris att strain with ts characteristics in vitro and an att phenotype in vivo. Vaccination studies in mice showed that a single dose of the B/Bris att candidate stimulated sterilizing immunity against lethal homologous challenge and complete protection against heterologous challenge. These studies show the potential of an alternative LAIV platform for the development of IBV vaccines. IMPORTANCE A number of issues with regard to the effectiveness of the LAIV vaccine licensed in the United States (FluMist) have arisen over the past three seasons (2013–2014, 2014–2015, and 2015–2016). While the reasons for the limited robustness of the vaccine-elicited immune response remain controversial, this problem highlights the critical importance of continued investment in LAIV development and creates an opportunity to improve current strategies so as to develop more efficacious vaccines. Our laboratory has developed an alternative strategy, the incorporation of 2 amino acid mutations and a modified HA tag at the C terminus of PB1, which is sufficient to attenuate the IBV. As a LAIV, this novel vaccine provides complete protection against IBV strains. The availability of attenuated IAV and IBV backbones based on contemporary strains offers alternative platforms for the development of LAIVs that may overcome current limitations.

scholarly journals Mouse-adapted influenza B virus for in vitro and in vivo assessment of therapeutic and preventive efficacy of antiviral drugs

2019 ◽  
Vol 11 (4) ◽  
pp. 53-64
Author(s):  
E. A. Prokopyeva ◽  
O. G. Kurskaya ◽  
M. V. Solomatina ◽  
I. A. Sobolev ◽  
Т. A. Murashkina ◽  
...  
Keyword(s):  
Antiviral Drugs ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Preventive Efficacy ◽  
In Vivo Assessment

scholarly journals A broadly protective therapeutic antibody against influenza B virus with two mechanisms of action

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Ning Chai ◽  
Lee R. Swem ◽  
Summer Park ◽  
Gerald Nakamura ◽  
Nancy Chiang ◽  
...  
Keyword(s):  
Human Monoclonal Antibody ◽  
Antiviral Effect ◽  
Therapeutic Benefit ◽  
Influenza B Virus ◽  
Influenza B ◽  
Lethal Challenge ◽  
Enrichment Technique ◽  
B Virus

Abstract Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion. After passage of the B/Brisbane/60/2008 virus in the presence of 46B8, we isolated three resistant clones, all harbouring the same mutation (Ser301Phe) in HA that abolishes 46B8 binding to HA at low pH. Interestingly, 46B8 is still able to protect mice against lethal challenge of the mutant viruses, possibly owing to its ability to mediate antibody-dependent cellular cytotoxicity (ADCC).

scholarly journals FluB-RAM and FluB-RANS: Genome re-arrangement as safe and efficacious live attenuated influenza B virus vaccines.

2021 ◽  
Author(s):  
Stivalis Cardenas-Garcia ◽  
C. Joaquín Cáceres ◽  
Aarti Jain ◽  
Ginger Geiger ◽  
Jong-Suk Mo ◽  
...  
Keyword(s):  
Natural Infection ◽  
The Elderly ◽  
Respiratory Pathogen ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Cellular Immune ◽  
And Control

Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated influenza virus vaccines (LAIVs) are thought to induce both humoral and cellular immune responses by mimicking a natural infection, but their effectiveness have recently come into question. Thus, the opportunity exists to find alternative approaches to improve overall influenza vaccine effectiveness. Two alternative IBV backbones were developed with re-arranged genomes, re-arranged M (FluB-RAM) and a re-arranged NS (FluB-RANS). Both re-arranged viruses showed temperature sensitivity in vitro compared to the WT type B/Bris strain, were genetically stable over multiple passages in embryonated chicken eggs and were attenuated in vivo in mice. In a prime-boost regime in naïve mice, both re-arranged viruses induced antibodies against HA with hemagglutination inhibition titers considered of protective value. In addition, antibodies against NA and NP were readily detected with potential protective value. Upon lethal IBV challenge, mice previously vaccinated with either FluB-RAM or FluB-RANS were completely protected against clinical disease and mortality. In conclusion, genome re-arrangement renders efficacious LAIV candidates to protect mice against IBV.

Reticulon 3-mediated Chk2/p53 activation suppresses hepatocellular carcinogenesis and is blocked by hepatitis B virus

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321386
Author(s):  
Shushu Song ◽  
Yinghong Shi ◽  
Weicheng Wu ◽  
Hao Wu ◽  
Lei Chang ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Dependent Manner ◽  
Mice Model ◽  
Calcium Dependent ◽  
B Virus ◽  
P53 Activation ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

ObjectiveDysfunction of endoplasmic reticulum (ER) proteins is closely related to homeostasis disturbance and malignant transformation of hepatocellular carcinoma (HCC). Reticulons (RTN) are a family of ER-resident proteins critical for maintaining ER function. Nevertheless, the precise roles of RTN in HCC remain largely unclear. The aim of the study is to examine the effect of reticulon family member RTN3 on HCC development and explore the underlying mechanisms.DesignClinical HCC samples were collected to assess the relationship between RTN3 expression and patients’ outcome. HCC cell lines were employed to examine the effects of RTN3 on cellular proliferation, apoptosis and signal transduction in vitro. Nude mice model was used to detect the role of RTN3 in modulating tumour growth in vivo.ResultsWe found that RTN3 was highly expressed in normal hepatocytes but frequently downregulated in HCC. Low RTN3 expression predicted poor outcome in patients with HCC in TP53 gene mutation and HBV infection status-dependent manner. RTN3 restrained HCC growth and induced apoptosis by activating p53. Mechanism studies indicated that RTN3 facilitated p53 Ser392 phosphorylation via Chk2 and enhanced subsequent p53 nuclear localisation. RTN3 interacted with Chk2, recruited it to ER and promoted its activation in an ER calcium-dependent manner. Nevertheless, the tumour suppressive effects of RTN3 were abrogated in HBV-positive cells. HBV surface antigen competed with Chk2 for RTN3 binding and blocked RTN3-mediated Chk2/p53 activation.ConclusionThe findings suggest that RTN3 functions as a novel suppressor of HCC by activating Chk2/p53 pathway and provide more clues to better understand the oncogenic effects of HBV.

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