Infection of rat osteoblasts with Junin virus promotes the expression of bone morphogenetic protein 6, an osteogenic differentiation inducer

AYALA PEÑA V.B; ARMIENTO N; FERNANDEZ BELL FANO; SANTILLAN G. E.; SCOLARO L. A.

INTERVIROLOGY

KARGER

Lugar: Basel; Año: 2019

0300-5526

virus (JUNV), causative agent of the argentine hemorrhagic fever (AHF), a zoonotic 27 disease of the central region of Argentina, belongs to the Arenaviridae family. JUNV infection is highly lethal in humans reaching up to 30% mortality when it is not treated by administration of immune plasma. In vitro replication of JUNV involves the modulation of several cell signalling pathways that contribute to an efficient production of viral progeny. In the present work we studied the capability of JUNV to infect primary cultures of rat osteoblasts (OBCs) and to modulate the expression of osteogenic genes. In addition, we evaluated the effect of purinergic agonists on viral replication. Infection of OBCs with JUNV (MOI 0.01 PFU/cell) showed a peak of infectivity, reaching 1.5 x 105 PFU/ml at the second day post infection although no cytopathic effect was detected by microscopic observation of the cultures. A marked restriction in multiplication was detected at day 7 p.i. that did not impair the establishment of a persistent stage of infection in OBCs. Analysis of mRNAs corresponding to osteogenic differentiation markers like alkaline phosphatase (ALP), bone sialo-protein (BSP) and bone morphogenetic proteins (BMPs) 4 and 6 in JUNV infected OBCs revealed that only the levels of BMP-6 were significantly higher (4,5 fold of increment) in JUNV infected cells in comparison with mock infected cells. JUNV infected OBCs treated with the purinergic agonists ATPγS, UTP, ADP or UDP showed diminished viral titter and a reduced expression of the viral nucleoprotein in comparison with infected untreated cells. Also, treatment with 10 μM ATPγS reduced the stimulation of BMP-6 expression induced by the virus. These data demonstrate that JUNV is capable of infecting OBCs and point out BMP-6 as a prospective antiviral molecule with potential use against JUNV.