scholarly journals Effects of Different Drug Combinations in Immunodeficient Mice Infected with an Influenza A/H3N2 Virus

2020 ◽  
Vol 8 (12) ◽  
pp. 1968
Author(s):  
Zeineb Mhamdi ◽  
Hugues Fausther-Bovendo ◽  
Olus Uyar ◽  
Julie Carbonneau ◽  
Marie-Christine Venable ◽  
...  
Keyword(s):  
Influenza A ◽  
Survival Rates ◽  
Resistance Mutation ◽  
Drug Combinations ◽  
H3n2 Virus ◽  
Prolonged Treatment ◽  
Immunodeficient Mice ◽  
Weight Losses ◽  
Multiple Dose Regimen ◽  
Improvement In Survival

The prolonged treatment of immunosuppressed (IS) individuals with anti-influenza monotherapies may lead to the emergence of drug-resistant variants. Herein, we evaluated oseltamivir and polymerase inhibitors combinations against influenza A/H3N2 infections in an IS mouse model. Mice were IS with cyclophosphamide and infected with 3 × 103 PFU of a mouse-adapted A/Switzerland/9715293/2013 (H3N2) virus. Forty-eight hours post-infection, the animals started oseltamivir, favipiravir or baloxavir marboxil (BXM) as single or combined therapies for 10 days. Weight losses, survival rates and lung viral titers (LVTs) were determined. The neuraminidase (NA) and polymerase genes from lung viral samples were sequenced. All untreated animals died. Oseltamivir and favipiravir monotherapies only delayed mortality (the mean day to death (MDD) of 21.4 and 24 compared to 11.4 days for those untreated) while a synergistic improvement in survival (80%) and LVT reduction was observed in the oseltamivir/favipiravir group compared to the oseltamivir group. BXM alone or in double/triple combination provided a complete protection and significantly reduced LVTs. Oseltamivir and BXM monotherapies induced the E119V (NA) and I38T (PA) substitutions, respectively, while no resistance mutation was detected with combinations. We found that the multiple dose regimen of BXM alone provided superior benefits compared to oseltamivir and favipiravir monotherapies. Moreover, we suggest the potential for drug combinations to reduce the incidence of resistance.

scholarly journals Neuraminidase gene homology contributes to the protective activity of influenza vaccines prepared from the influenza virus library

2014 ◽  
Vol 95 (11) ◽  
pp. 2365-2371 ◽  
Author(s):  
Ahmad M. Haredy ◽  
Hiroshi Yamada ◽  
Yoshihiro Sakoda ◽  
Masatoshi Okamatsu ◽  
Naoki Yamamoto ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Survival Rates ◽  
Influenza Vaccines ◽  
H3n2 Virus ◽  
Protective Activity ◽  
Virus Clearance ◽  
Ha Gene ◽  
Gene Homology ◽  
Antibody Titres

Whole-virus (WV) vaccines from influenza A/duck/Hokkaido/77 (H3N2), and its reassortant strains H3N4, H3N5 and H3N7, which have the same haemagglutinin (HA) gene but different neuraminidase (NA) genes, were prepared from our influenza virus library. Mice were intranasally immunized with equivalent doses of each vaccine (1–0.01 µg per mouse). All of the mice that received the highest dose of each vaccine (1 µg per mouse) showed equivalent high HA-inhibiting (HI) antibody titres and survived the H3N2 challenge viruses. However, mice that received lower doses of vaccine (0.1 or 0.01 µg per mouse) containing a heterologous NA had lower survival rates than those given the H3N2-based vaccine. The lungs of mice challenged with H3N2 virus showed a significantly higher virus clearance rate when the vaccine contained the homologous NA (N2) versus a heterologous NA, suggesting that NA contributed to the protection, especially when the HI antibody level was low. These results suggested that, even if vaccines prepared for a possible upcoming pandemic do not induce sufficient HI antibodies, WV vaccines can still be effective through other matched proteins such as NA.

scholarly journals Combination Therapy with Oseltamivir and Favipiravir Delays Mortality but Does Not Prevent Oseltamivir Resistance in Immunodeficient Mice Infected with Pandemic A(H1N1) Influenza Virus

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 610 ◽  
Author(s):  
Mariana Baz ◽  
Julie Carbonneau ◽  
Chantal Rhéaume ◽  
Marie-Hélène Cavanagh ◽  
Guy Boivin
Keyword(s):  
Influenza Virus ◽  
Combination Therapy ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Lethal Dose ◽  
Survival Rates ◽  
Oseltamivir Resistance ◽  
Immunodeficient Mice ◽  
Influenza A H1n1 ◽  
Viral Titers

Immunosuppressed individuals can shed influenza virus for prolonged periods of time, leading to the frequent emergence of antiviral resistance. We evaluated the benefits of oseltamivir and favipiravir combination therapy compared to single antiviral agents and monitored the emergence of drug-resistant variants in a pharmacologically immunosuppressed mouse model infected with the A(H1N1) pandemic influenza virus. C57BL/6 mice were immunosuppressed with cyclophosphamide and infected with a lethal dose of pandemic influenza A(H1N1) virus. Forty-eight hours post-infection, mice were treated with oseltamivir (20 mg/kg), favipiravir (20 or 50 mg/kg) or both agents BID for 5 or 10 days. Body weight losses, survival rates, lung viral titers, cytokine levels and emergence of resistant viruses were evaluated. Treatment of immunosuppressed mice with high (50 mg/kg) but not low (20 mg/kg) doses of favipiravir in combination with oseltamivir (20 mg/kg) significantly delayed mortality and reduced lung viral titers compared to treatment with a single drug regimen with oseltamivir but did not prevent the emergence of oseltamivir-resistant H275Y neuraminidase variants. Combination therapy with oseltamivir and favipiravir should be considered for evaluation in clinical trials.

A 75-year-old woman with seasonal influenza A (H3N2) virus infection and diarrhea

2010 ◽  
Vol 48 (4) ◽  
pp. 231-233 ◽  
Author(s):  
Martin C.W. Chan ◽  
Nelson Lee ◽  
Rity Y.K. Wong ◽  
Wing-Shan Ho ◽  
Joseph J.Y. Sung
Keyword(s):  
Virus Infection ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H3n2 Virus

scholarly journals Vaccination against Human Influenza A/H3N2 Virus Prevents the Induction of Heterosubtypic Immunity against Lethal Infection with Avian Influenza A/H5N1 Virus

PLoS ONE ◽  
2009 ◽  
Vol 4 (5) ◽  
pp. e5538 ◽  
Author(s):  
Rogier Bodewes ◽  
Joost H. C. M. Kreijtz ◽  
Chantal Baas ◽  
Martina M. Geelhoed-Mieras ◽  
Gerrie de Mutsert ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
H5n1 Virus ◽  
H3n2 Virus ◽  
Human Influenza ◽  
Lethal Infection ◽  
Heterosubtypic Immunity

scholarly journals Environmental Levels of the Antiviral Oseltamivir Induce Development of Resistance Mutation H274Y in Influenza A/H1N1 Virus in Mallards

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24742 ◽  
Author(s):  
Josef D. Järhult ◽  
Shaman Muradrasoli ◽  
John Wahlgren ◽  
Hanna Söderström ◽  
Goran Orozovic ◽  
...  
Keyword(s):  
Influenza A ◽  
H1n1 Virus ◽  
Resistance Mutation ◽  
Development Of Resistance ◽  
Influenza A H1n1

Rapid diagnosis of influenza A infection by direct immunofluorescence of nasopharyngeal aspirates in adults

1979 ◽  
Vol 9 (6) ◽  
pp. 688-692
Author(s):  
J A Daisy ◽  
F S Lief ◽  
H M Friedman
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Virus Isolation ◽  
Fluorescent Antibody ◽  
Positive Culture ◽  
H3n2 Virus ◽  
Direct Immunofluorescence ◽  
The One ◽  
Immunofluorescent Test ◽  
Culture Negative

The efficacy for direct immunofluorescence of a commercial conjugate for influenza A virus prepared against whole A/Udorn (H3NS) virus was studied. The conjugate was specific for influenza A virus, but its sensitivity varied depending upon the strain of influenza A tested. Nasopharyngeal aspirates collected from 25 patients during an outbreak of influenza were examined for viral antigen with the conjugates and inoculated onto monkey kidney (MK) cells for virus isolation. Fifteen patients had isolates for influenza A/USSR/90/77 (H1N1); nasopharyngeal secretions were fluorescent antibody positive in 12. Fluorescent antibody was copositive with culture in 11/15 patients (73.3%) and conegative in 9/10 (90%). The one fluorescent antibody-positive, culture-negative patient had negative serology for influenza A and the fluorescent antibody result was considered to be a false positive. At a 1:10 dilution, the conjugate stained nasopharyngeal and MK cells infected with A/USSR (H1N1) 2 to 3+, whereas cells infected with H3N2 virus stained 4+. A conjugate made specifically against the ribonucleoprotein antigen, which is universal to all influenza A strains, may improve the sensitivity of the direct immunofluorescent test.

scholarly journals Pre-exposure with influenza A virus A/WSN/1933(H1N1) resulted in viral shedding reduction from pigs challenged with either swine H1N1 or H3N2 virus

2019 ◽  
Vol 228 ◽  
pp. 26-31 ◽  
Author(s):  
Zhao Wang ◽  
Jieshi Yu ◽  
Milton Thomas ◽  
Chithra C. Sreenivasan ◽  
Ben M. Hause ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H3n2 Virus ◽  
Viral Shedding

scholarly journals Multiple Influenza A (H3N2) Mutations Conferring Resistance to Neuraminidase Inhibitors in a Bone Marrow Transplant Recipient

2014 ◽  
Vol 58 (12) ◽  
pp. 7188-7197 ◽  
Author(s):  
Alireza Eshaghi ◽  
Sarah Shalhoub ◽  
Paul Rosenfeld ◽  
Aimin Li ◽  
Rachel R. Higgins ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Therapy ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Marrow Transplant ◽  
Viral Fitness ◽  
H3n2 Virus ◽  
Resistance Mutations ◽  
Depth Analysis ◽  
Resistant Strains

ABSTRACTImmunocompromised patients are predisposed to infections caused by influenza virus. Influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistant strains. Characterization of neuraminidase (NA) inhibitor (NAI)-resistant strains of influenza A virus is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified an NAI-resistant strain of influenza A (H3N2) virus in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance, including transient R292K and Q136K substitutions and a sustained E119K (N2 numbering) substitution in the NA protein emerged during prolonged antiviral therapy. In addition, a combination of a 4-amino-acid deletion at residues 245 to 248 (Δ245-248) accompanied by the E119V substitution occurred, causing resistance to or reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir). Resistant variants within a pool of viral quasispecies arose during combined antiviral treatment. More research is needed to understand the interplay of drug resistance mutations, viral fitness, and transmission.

scholarly journals Natural co-infection of influenza A/H3N2 and A/H1N1pdm09 viruses resulting in a reassortant A/H3N2 virus

2015 ◽  
Vol 73 ◽  
pp. 108-111 ◽  
Author(s):  
Sareth Rith ◽  
Savuth Chin ◽  
Borann Sar ◽  
Phalla Y ◽  
Srey Viseth Horm ◽  
...  
Keyword(s):  
Influenza A ◽  
H3n2 Virus
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