Antiviral protection by vesicular stomatitis virus-specific antibodies in alpha/beta interferon receptor-deficient mice

Abstract

The role of innate, alpha/beta interferon (IFN-␣/␤)-dependent protection versus specific antibody-mediated protection against vesicular stomatitis virus (VSV) was evaluated in IFN-␣/␤ receptor-deficient mice (IFN-␣/␤ R 0 / 0 mice). VSV is a close relative to rabies virus that causes neurological disease in mice. In contrast to normal mice, IFN-␣/␤ R 0 / 0 mice were highly susceptible to infection with VSV because of ubiquitous high viral replication. Adoptive transfer experiments showed that neutralizing antibodies against the glycoprotein of VSV (VSV-G) protected these mice efficiently against systemic infection and against peripheral subcutaneous infection but protected only to a limited degree against intranasal infection with VSV. In contrast, VSV-specific T cells or antibodies specific for the nucleoprotein of VSV (VSV-N) were unable to protect IFN-␣/␤ R 0 / 0 mice against VSV. These results demonstrate that mice are extremely sensitive to VSV if IFN-␣/␤ is not functional and that under these conditions, neutralizing antibody responses mediate efficient protection, but apparently only against extraneuronal infection.

Plasmacytoid Dendritic Cell Ablation Impacts Early Interferon Responses and Antiviral NK and CD8+ T Cell Accrual

“…Not surprisingly, the defect of CTL accumulation in pDC-depleted mice infected with VSV-OVA had no obvious impact on viral loads in the brain at later time points (data not shown), because VSV clearance is mainly dependent on Ab responses (Steinhoff et al, 1995), which did not vary between control and pDC-depleted mice (data not shown). However, pDCmediated accumulation of CTLs may be essential in the control of other experimental infections, such as murine hepatitis virus (MHV), herpes simplex virus 2 (HSV-2), and respiratory syncytial virus (RSV), in which pDC depletion impairs host antiviral responses (Cervantes-Barragan et al, 2007;Smit et al, 2006;Thompson and Iwasaki, 2008;Wang et al, 2006).…”

The role of IL-12, IL-23 and IFN-γ in immunity to viruses

“…IFN-␣/␤ is considered to play a major role in antiviral defense [152]. For experimental infections, anti-IFN␣/␤ antibody-treated mice [152] and IFN␣/␤ receptor KO mice [104,112,[153][154][155][156][157], as well as mice deficient in both IFN␣/␤ and IFN-␥ receptors [5,55], STAT1 [158,159] and STAT2 [160] showed marked sensitivity to a broad range of DNA and RNA viruses. However, the IL-12/IL-23 and IFN-␥ axis is interconnected with IFN␣/␤ in the antiviral defense.…”

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

“…Finally, we assessed the protective effect of mtdVSV-based ZIKV vaccines in A129 mice which lack the type-I interferon receptor (IFNAR). These mice have been shown to be highly permissive for both ZIKV 47,48 and VSV infection 49,50 . In fact, A129 mice are so susceptible to wild-type VSV infection that a dose of 50 PFU is lethal 50 .…”