THE DYNAMICS OF ORTHOHANTAVIRUS HANTAAN STRAINS REPLICATION ON THE MODEL OF MOUSE PERITONEAL MACROPHAGES

Orthohantaviruses (Orthohantavirus genus, Hantaviridae family) are the causative agents of a widespread natural focal infection in the  Russian Federation, hemorrhagic fever with renal syndrome (HFRS).  An important role in the persistence of orthohantavirus in reservoir  hosts among other immunological responses, as well as in the  spread of the virus in the infected organism, is played by infected  macrophages, which, along with the vascular endothelium, are the main targets for orthohantaviruses.

The aim of our study was to investigate the characteristics of replication of orthohantavirus Hantaan strains isolated from  Apodemus mice and detect the influence of different values of  multiplicity of infection (MOI) on replication dynamics of orthohantaviruses on cell culture.

Materials and methods. We used 4 strains of Hantaan virus, isolated from A. agrarius (n = 2) and A. peninsulae (n = 2), captured in the different areas of Primorsky Krai of Russia. The  modeling of infection was performed on the primary cell culture of  mouse peritoneal macrophages with different MOI (from 10 to 0.1).  The assessing of infection was conducted via indirect fluorescent  antibody assay, and results were expressed as rate of antigen- positive cells per all cells in the field of vision. 

Results. Common dynamics of orthohantavirus infection on this in vitro model was characterized by periodically increased rates of  infected cells after 2, 4, 6 и 8 hours post infection (p.i.). Replication  of A. agrarius-borne strains was more intensive compare with  viruses, isolated from A. peninsulae, in the time point 4 hour p.i. on  the background the same MOI the statistically significant difference  of rate of antigen-positive cell 24.9 ± 2.38 % vs 15.2 ± 1.87 % (t =  3.20; p = 0.001414) was observed. Additionally, the decrease of MOI was followed by determined decrease of replication effectivity.

Conclusion. The results of our study showed the significant phenotyping heterogeneity of orthohantavirus Hantaan strains,  isolated from Apodemus mice, resulting in different rates of  replication in the culture of mouse peritoneal macrophages.

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