Studies of Influenza A/H1N1 A/Tomsk/13/2010 Virus Topology during Development of Infectious Process in Mammals.

Influenza A/H1N1 A/Tomsk/13/2010 virus registered in Siberia in 2010 proved to be an extremely pathogenic strain. Dynamic study of the topology of this influenza virus strain in the lungs, liver, kidneys, lymph nodes, and great vessels of infected mice was carried out. Influenza A virus was detected by immunohistochemical methods in cells of different histogenesis in all the studied organs throughout the observation period (days 1-30 postinfection), which indicated effective replication and long persistence of influenza A/H1N1 A/Tomsk/13/2010 virus in mammalian cells.

Expression of profibrotic growth factors and their receptors by mouse lung macrophages and fibroblasts under conditions of acute viral inflammation in influenza A/H5N1 virus.

Morphological signs of early interstitial fibrosis, developing under conditions of acute viral inflammation (postinfection days 1-14), were observed in C57Bl/6 mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus. The development of fibrosis was confirmed by an increase in the number of lung cells expressing TNF-α. These changes were recorded in the presence of a many-fold increase in the counts of macrophages and fibroblasts expressing FGF, EGF, and their receptors.

Role of matrix metalloproteinases and their inhibitor in the development of early pulmonary fibrosis in mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus.

High levels of macrophages and fibroblasts expressing MMP-2, MMP-9, and MMP-10 against the background of progressing early fibrosis of the lungs (manifesting in an increase in volume density of type I, III, IV, and VI collagens) were found in C57Bl/6 mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus. Progressing fibrosis of the lungs in infected mice was associated with imbalance of collagen synthesis and degradation processes conjugated with high levels of macrophages and fibroblasts expressing TIMP-2.

Morphofunctional characteristics of fibroblasts and fibrogenesis in the lungs of mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus.

Mice C57Bl/6 were intranasally infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus. The expression of influenza A virus antigen in the lung interstitium fibroblasts was recorded during all periods of the study (on days 1-14 after infection), the maximum expression on days 1 and 3. On day 1, the volume density of collagen fibers in the lungs was 3-fold higher than in intact animals; by day 14 it increased almost 15-fold. The numerical density of PCNA(+)fibroblasts increased almost 2-fold from day 1 to day 10; "fibroplastic activity" of fibroblasts increased more than 3-fold.

Structural and functional changes in pulmonary macrophages and lungs of mice infected with influenza virus A/H5N1 A/goose/Krasnoozerskoye/627/05.

C57Bl/6 mice were intranasally infected with influenza virus A/H5N1 A/goose/Krasnoozerskoye/627/05. The mortality rate of animals reached 70% on day 14 of the disease. The lungs of animals were characterized by necroses, destruction of vessels, hemorrhagic and thrombotic complications, edematous syndrome, and early fibrosis of the interstitium. On days 6-10 after infection, fibrosis was found in the zones of postnecrotic inflammatory infiltration. The expression of lysozyme and myeloperoxidase by pulmonary macrophages was initially increased, but decreased on day 10 of the study. The number of cathepsin D-expressing macrophages was elevated up to the 10th day of examination.