Lethal Nipah Virus Infection Induces Rapid Overexpression of CXCL10

Mathieu, Cyrille; Guillaume, Vanessa; Sabine, Amélie; Ong, Kien Chai; Wong, Kum Thong; Legras-Lachuer, Catherine; Horvat, Branka

CXCL10 is a secreted polypeptide of 10 kDa that was first identified as an early response gene induced after interferon gamma treatment in a variety of cells, and was thus named interferon gamma-inducible peptide, IP-10 [22, 23] . Furthermore, it was shown that interferon alpha could also induce CXCL10 in primary cultured neurons [24] and seminiferous tubules [25] . In addition to interferons, HIV envelope glycoprotein gp120 was shown to induce expression of CXCL10 in brains of mice [26] . HIV Tat protein can also induce CXCL10 in astrocytes [27] . Furthermore, CXCL10 is expressed early in the CNS in response to a wide variety of viruses [11, 13, 28, 29, 30] . Our results demonstrate that NiV-infection induces rapidly production of CXCL10 in primary endothelial cells. As production of interferon gamma by these cells is contested, it is possible that the generation of CXCL10 is either a direct effect of NiV proteins or is induced via NiV-activation of interferon beta, following infection. Moreover, our results demonstrate induction of CXCL10 in vivo in different organs of NiV-infected hamsters, as well as in patients that succumbed to lethal NiV-infection, thus revealing an important association between NiV-infection and CXCL10 production. Although endothelial cells were clearly secreting this chemokine, the perivascular inflammatory cells and some neurons are most probably participating in the production of CXCL10 as well.