Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice

Pneumonia often occurs as secondary infection post influenza disease and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug triazavirine is licensed in Russia for the treatment and prophylaxis of acute respiratory infections, including influenza A and B viruses. In the present study, we investigated the efficacy of triazavirine in a mouse model of secondary Staphylococcus aureus pneumonia following A/California/04/2009 (H1N1)pdm09 influenza virus infection. We also performed a study of the efficacy of triazavirine against the A/California/04/2009 (H1N1)pdm09 lethal influenza infection in mice. In this model, triazavirine at the dose of 25 mg/kg/day significantly enhanced the survival of animals (60% compared to 20%) and the mean survival time to death, prevented weight loss, and reduced viral titer in the lungs of mice infected with influenza virus. At doses of 50 and 100 mg/kg/day, triazavirine was highly effective in the treatment of the secondary bacterial pneumonia following influenza infection in mice. At these doses, triazavirine protected 67-75% of animals against death, increased the mean survival time to death by twofold, and reduced the virus titer by 2.2-3.0 log10TCID50/ml compared to the mice in the control group. These findings suggest the possible benefit of triazavirine treatment in reducing post influenza pneumonia incidence in humans.Pneumonia often occurs as secondary infection post influenza disease and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug triazavirine is licensed in Russia for the treatment and prophylaxis of acute respiratory infections, including influenza A and B viruses. In the present study, we investigated the efficacy of triazavirine in a mouse model of secondary Staphylococcus aureus pneumonia following A/California/04/2009 (H1N1)pdm09 influenza virus infection. We also performed a study of the efficacy of triazavirine against the A/California/04/2009 (H1N1)pdm09 lethal influenza infection in mice. In this model, triazavirine at the dose of 25 mg/kg/day significantly enhanced the survival of animals (60% compared to 20%) and the mean survival time to death, prevented weight loss, and reduced viral titer in the lungs of mice infected with influenza virus. At doses of 50 and 100 mg/kg/day, triazavirine was highly effective in the treatment of the secondary bacterial pneumonia following influenza infection in mice. At these doses, triazavirine protected 67-75% of animals against death, increased the mean survival time to death by twofold, and reduced the virus titer by 2.2-3.0 log10TCID50/ml compared to the mice in the control group. These findings suggest the possible benefit of triazavirine treatment in reducing post influenza pneumonia incidence in humans

Influenza virus infection and postviral bacterial pneumonia pathogenesis induced by different subtypes of influenza virus in mice

Secondary bacterial infections after influenza virus infection further increase morbidity and mortality due to influenza. Despite of seasonal influenza vaccination, antiviral drugs and antibiotics are widely used in viral/bacterial pneumonia therapy. Therefore, further comprehensive study of the infection pathogenesis is relevant. Murine models for influenza virus infection were reproduced with different virus subtypes A/California/04/2009MA (pandemic H1N1 2009), A/Puerto Rico/8/34 (H1N1) and A/Aichi/2/69 (H3N2), Anadyr/177/2009 (H1N1) and for post-influenza bacterial pneumonia caused by the Gram-positive Staphylococcus aureus. After the infection occurs, its pathogenic features were detected by daily monitoring the mortality (survival) and morbidity rate (body weight loss) and, in addition, viral pathogenesis also was evaluated by assessing virus replication (viral titer) and humoral immune responses (production of pro- and anti-inflammatory cytokines) in respiratory tract of infected mice including during antiviral (oseltamivir) and antibacterial (cefuroxime) therapy. Mortality and virus titer in the infected mice did not differ significantly between the groups of different influenza A virus subtypes. However, production of cytokines (IL-10, IFNg, TNFa) and weight gain proved to be different. Mortality of the mice reached 100% after secondary bacterial infection, whereas IFNg and TNFa levels in mice lung increased reached maximal values in the treated groups. Viral subtype A/California/04/2009MA of influenza A was most pathogenic in mouse model of secondary bacterial pneumonia. Antiviral and antibacterial treatment caused a decrease in mortality, reduced viral titers in lungs, and retain body weight gain of mice. According to these points, the treatment groups did not significantly differ from each other. At the same time, it should be noted that the cytokine production significantly decreased in the treated groups, and IL-10 and IFNg levels in lungs were different, that may be due to therapeutic mechanisms of these drugs. Thus, antiviral therapy for influenza infection and combination therapy for viralbacterial pneumonia can be an effective tool to reduce mortality of influenza

The safety of attenuated and recombinant nasal influenza vaccines in terms of the development of secondary bacterial superinfection

Introduction. Influenza is a severe viral disease. The most common post-influenza complication is pneumonia. Earlier, we developed an experimental mouse model of viralbacterial pneumonia induced by successive infection with influenza virus and St. aureus, in which lethal synergy between pathogens observed in epidemiological observations was detected.Aim. To study the effect of the administration of intranasal vaccines, followed by infection with St. pneumoniae on the development and completion of the disease.Materials and methods. The animals were immunized intranasal with a strain of attenuated cold-adapted live influenza vaccine A/17/California/2009/38 (H1N1)pdm09 (LAIV) and a recombinant vaccine based on virus-like particles HA(Puerto Rico/8/34)- Gag (VLPs). Control groups of animals were infected with virulent strains of influenza virus A/ California/04/2009 (H1N1)pdm09 or A/Puerto Rico /8/34 (H1N1). On the fifth day after intranasal immunization with the vaccine preparations and infection with pathogenic strains, animals were subjected to bacterial infection with a strain of St. pneumoniae. The presence of synergism of vaccine or viral agent with bacterial infection was assessed by survival and weight loss of animals, virus titer and density of bacteria in nasopharyngeal washes and lungs.Results. It was shown that immunization with vaccine preparations did not lead to increased sensitivity of mice to bacterial infection. Elimination of bacteria from the lungs and nasopharynx in groups immunized with vaccine preparations corresponded to the dynamics in the group of animals immunized by PBS.Discussion. The results obtained indicate the safety of intranasal immunization with LAIV A/17/California/2009/38 (H1N1)pdm09 and virus-like particles HA (Puerto Rico/8/34)- Gag (VLPs) in terms of enhancing secondary bacterial superinfection caused by St. pneumoniae.Conclusion. The studied vaccines successfully blocked infections in the lower respiratory tract

INDUCTION OF SECONDARY BACTERIAL PNEUMONIA IN MICE INFECTED WITH PANDEMIC AND LABORATORY STRAINS OF THE H1N1 INFLUENZA VIRUS

Aim. In this study we developed and characterized a mouse model of secondary S. aureus and S. pneumoniae pneumonia following influenza virus infection with H1N1 pandemic and laboratory strains and their reassortment. Materials and methods. BALB/с mice were infected intranasally with A/California/04/2009/(H1N1 pndm), A/Puerto Rico/8/34 or their reassortment NIBRG-121xp followed by different strains of S. аureus и S. pneumoniae. The pathogenicity of infection was assessed by mouse survival and weight change, viral titre and bacterial count in the lungs. Results. It was shown that the infection of mice with three strains of the H1N1 influenza virus with a comparable level of pathogenicity leads to a different severity of secondary bacterial infection. The mouse adapted A/California/04/2009 pandemic strain possessed the greatest ability to alter antibacterial immunity. Conclusion. An experimental model of post-influenza bacterial pneumonia utilizing three strains of the H1N1 influenza virus and various strains of S. aureus or S. pneumoniae was established. The ability of viruses to provoke bacterial superinfection of different severity is characterized

Activity of compounds containing echinochrome A against herpes simplex virus type 2 <i>in vitro</i> and <i>in vivo</i>

The aim of the work was to study the activity of echinochrome A, a naphthoquinoid pigment from sea urchins, and its antioxidant composition against herpes simplex virus type 2 (HSV-2) in vitro and in vivo.Materials and methods. Strain HSV-2 (G ATCC VR-734) was grown in Vero cells. The cytotoxic and anti-HSV-2 activity of the compounds was assessed in vitro by the cell viability and by cytopathic effect inhibition of virus using MTT test. The efficacy of compounds in mice model of vaginitis caused by HSV-2 was determined by the average lifetime, body weight and viral load changes.Results and discussion. The antioxidant composition (echinochrome A, ascorbic acid and α-tocopherol (5:5:1)), showed a higher antiviral efficacy than echinochrome A alone. Oral administration of the antioxidant composition protected 90% of the infected mice against death and reduced vaginal viral loads. The antiviral activity of echinochrome A and the antioxidant composition is probably due to the virus-inhibiting activity of the compounds and their antioxidant properties.Conclusion. The results obtained allow considering the tested compounds as promising agents with antiviral properties