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Ideally, an oncolytic virus will replicate preferentially in malignant cells, have the ability to treat disseminated metastases, and ultimately be cleared by the patient. Here we present evidence that the attenuated vesicular stomatitis strains, AV1 and AV2, embody all of these traits. We uncover the mechanism by which these mutants are selectively(More)
Interferons (IFNs) are produced in response to virus infection and induce an antiviral state in virtually all cell types. In addition to upregulating the transcription of genes that inhibit virus replication, type I (or -α/β) IFNs also act to orchestrate the adaptive immune response to virus infection. Recently a new family of antiviral cytokines, the type(More)
We have studied the pathogenesis of influenza virus infection in mice that are unable to respond to type I or II interferons due to a targeted disruption of the STAT1 gene. STAT1-/- animals are 100-fold more sensitive to lethal infection with influenza A/WSN/33 virus than are their wild-type (WT) counterparts. Virus replicated only in the lungs of WT(More)
The V protein of the Paramyxovirus simian virus 5 (SV5) is a multifunctional protein containing an N-terminal 164 residue domain that is shared with the P protein and a distinct C-terminal domain that is cysteine-rich and which is highly conserved among Paramyxoviruses. We report the recovery from Vero cells [interferon (IFN) nonproducing cells] of a(More)
Parainfluenza virus type 5 (PIV5), formerly known as simian virus 5 (SV5), is a non-segmented negative strand RNA virus that offers several advantages as a vaccine vector. PIV5 infects many cell types causing little cytopathic effect, it replicates in the cytoplasm of infected cells, and does not have a DNA phase in its life cycle thus avoiding the(More)
The type I alpha/beta interferons (IFN-α/β) are known to play an important role in host defense against influenza A virus infection, but we have now discovered that the recently identified type III IFNs (IFN-λ) constitute the major response to intranasal infection with this virus. Type III IFNs were present at much higher levels than type I IFNs in the(More)
Respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, is a major clinical problem causing yearly epidemics of severe lower airway disease in both infants and the elderly. Attempts at vaccination have been frustrated by both the poor immunogenicity of this virus, and the severe immunopathology observed in early vaccine trials. Primary(More)
Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct(More)
SVap15/21, a strain of Sindbis virus (SV) derived from our standard laboratory strain of SV (SVstd) after repeated passage on Aedes albopictus cells, grows normally in mosquito cells but is host restricted (hr) in vertebrate cells. It is also temperature sensitive (ts) and produces pinpoint plaques on vertebrate cells (sp). E2 glycoprotein of SVstd differs(More)
Formalin-inactivated respiratory syncytial virus (RSV) vaccine preparations have been shown to cause enhanced disease in naive hosts following natural infection. In this study we demonstrate a similar pattern of enhanced disease severity following primary RSV infection of IFN-nonresponsive STAT1(-/-) mice. STAT1(-/-) mice showed markedly increased illness(More)