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Updated: Aug 15, 2026
Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
Published on: June 27, 2020
Polymer-bound 6' sialyl-N-acetyllactosamine protects mice infected by influenza virus
A S Gambaryan1, E Y Boravleva, T Y Matrosovich
1M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, 142782 Moscow, Russia.
Abstract:
To develop a mouse model for testing receptor attachment inhibitors of human influenza viruses, the human clinical virus isolate in MDCK cells A/NIB/23/89M (H1N1) was adapted to mice by serial passaging through mouse lungs. The adaptation enhanced the viral pathogenicity for mice, but preserved the virus receptor binding phenotype, preferential binding to 2-6-linked sialic acid receptors and low affinity for 2-3-linked receptors. Sequencing of the HA gene of the mouse-adapted virus A/NIB/23/89-MA revealed a loss of the glycosylation sites in positions 94 and 163 of HA1 and substitutions 275Asp-->Gly in HA1 and 145Asn-->Asp in HA2. The four mouse strains tested differed significantly in their sensitivity to A/NIB/23/89-MA with the sensitivity increasing in the order of BALB/cJCitMoise, C57BL/6LacSto, CBA/CaLacSto and A/SnJCitMoise strains. Testing of protective efficacy of the polyacrylamide conjugate bearing Neu5Acalpha2-6Galbeta1-4GlcNAc trisaccharide under conditions of lethal or sublethal virus infection demonstrated a strong protective effect of this preparation. In particular, aerosol treatment of mice with the polymeric attachment inhibitor on 24-110 h after infection completely prevented mortality in sensitive animals and lessened disease symptoms in more resistant mouse strains.
Insights
A mouse model was developed for testing influenza virus inhibitors. A novel polymeric attachment inhibitor demonstrated strong protection against lethal and sublethal infections in mice.
Area of Science:
- Virology
- Immunology
- Drug Development
Background:
- Developing mouse models is crucial for studying human influenza viruses and testing antiviral therapies.
- Understanding influenza virus receptor binding is key to developing effective inhibitors.
Purpose of the Study:
- To create a mouse model for evaluating receptor attachment inhibitors of human influenza viruses.
- To assess the efficacy of a specific polymeric attachment inhibitor against influenza virus infection in mice.
Main Methods:
- Adaptation of a human influenza virus isolate (A/NIB/23/89M, H1N1) to mice through serial lung passaging.
- Sequencing of the hemagglutinin (HA) gene to identify adaptive mutations.
- Testing the sensitivity of different mouse strains to the adapted virus.
- Evaluating the protective efficacy of a polyacrylamide conjugate bearing a Neu5Acalpha2-6Galbeta1-4GlcNAc trisaccharide via aerosol treatment.
Main Results:
- The mouse-adapted virus (A/NIB/23/89-MA) retained human influenza virus receptor binding properties.
- Significant differences in mouse strain sensitivity to the adapted virus were observed.
- Aerosol administration of the polymeric attachment inhibitor completely prevented mortality in sensitive mice and reduced disease severity in resistant strains.
Conclusions:
- The developed mouse model is suitable for testing influenza virus receptor attachment inhibitors.
- The polymeric attachment inhibitor shows significant therapeutic potential against influenza virus infections.
