Virus- and cell type-specific effects in orthohantavirus infection

Area of Science:

• Virology
• Cell Biology
• Pathology

Background:

• Orthohantaviruses Hantaan (HTNV) and Puumala (PUUV) cause hemorrhagic fever with renal syndrome (HFRS), characterized by renal failure.
• Orthohantaviral N protein is crucial for replication in renal cells, but its behavior in human renal cells is poorly understood.

Purpose of the Study:

• To investigate orthohantaviral infection in different human renal cell types.
• To compare the replication, N protein localization, particle release, and cytoskeleton modulation of HTNV and PUUV in human renal cells versus Vero E6 cells.

Main Methods:

• Infection of human renal cells and Vero E6 cells with HTNV and PUUV.
• Analysis of N protein localization (punctate vs. filamentous patterns).
• Assessment of particle release mechanisms and actin/microtubule cytoskeleton involvement.
• Evaluation of cytoskeletal rearrangements, particularly in podocytes.

Main Results:

• HTNV N protein showed both punctate and filamentous patterns; its release depended on intact actin/microtubules.
• PUUV N protein exhibited a punctate pattern; its release was independent of the actin cytoskeleton.
• HTNV infection caused more pronounced cytoskeletal rearrangements in podocytes than PUUV.
• Vero E6 cells showed no virus-specific differences, with strictly punctate N protein patterns, independent release, and no cytoskeletal changes.

Conclusions:

• Human renal cells exhibit distinct orthohantavirus replication patterns and induce virus-specific cytoskeletal changes.
• Vero E6 cells do not accurately reflect orthohantavirus behavior in human renal cells.
• Selecting appropriate cell culture models is critical for studying orthohantavirus pathogenicity and pathogenesis.