Novel Viral Disease Control Strategy: Adenovirus Expressing Alpha Interferon Rapidly Protects Swine from Foot-and-Mouth Disease

Abstract

We have previously shown that replication of foot-and-mouth disease virus (FMDV) is highly sensitive to alpha/beta interferon (IFN-␣/␤). In the present study, we constructed recombinant, replication-defective human adenovirus type 5 vectors containing either porcine IFN-␣ or IFN-␤ (Ad5-pIFN␣ or Ad5-pIFN␤). We demonstrated that cells infected with these viruses express high levels of biologically active IFN. Swine inoculated with 10 9 PFU of a control Ad5 virus lacking the IFN gene and challenged 24 h later with FMDV developed typical signs of foot-and-mouth disease (FMD), including fever, vesicular lesions, and viremia. In contrast, swine inoculated with 10 9 PFU of Ad5-pIFN␣ were completely protected when challenged 24 h later with FMDV. These animals showed no clinical signs of FMD and no viremia and did not develop antibodies against viral nonstructural proteins, suggesting that complete protection from infection was achieved.

Over-expressed human divalent metal transporter 1 is involved in iron accumulation in MES23.5 cells

“…Because the infection does not interfere with the host genome, Adeasy system shows a low risk to induce alteration of the host DNA. Therefore, it has been wildly used to deliver gene expression (Chinsangaram et al, 2003;Wesley et al, 2004;Mascola et al, 2005). After its infection of MES23.5 cells, a significant increase in intracellular iron levels was observed, which is in agreement with other studies conducted in the COS-7 cells and CHO cells (Worthington et al, 2000;Zhang et al, 2000).…”

Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus

“…Thus far, we have demonstrated that inoculation of mice with VRP-GFP induced a strong protective antiviral response against FMDV which correlated with increased levels of IFN-␣ in serum. This is in accordance with the demonstrated antiviral and protective effect of type I IFN against FMDV in the natural host (4,9,10). To confirm the antiviral effect of IFN-␣ against FMDV in the mouse model, we treated groups of five mice with 10 4 U of muIFN-␣ followed by challenge with 5 ϫ 10 4 PFU of FMDV A24 at 4 or 18 h after treatment.…”

“…The pVEK replicon vector is based on the current investigational new drug (IND) VEE virus vaccine (TC-83) (18,23). The poIFN-␣ and GFP genes were PCR amplified from existing DNA plasmids (9,24). Each PCR product coded for XbaI restriction sites at the 5= and 3= end.…”

“…The Ad5-Blue, Ad5-VSVG (containing the glycoprotein gene of vesicular stomatitis virus-NJ), and Ad5-poIFN-␣ vectors were constructed as previously described (9,26). Ad5-GFP and an Ad5 vector containing a small interfering RNA (siRNA) directed against GFP (Ad5-siGFP) were produced using the pAd5-Blue direct ligation system (26).…”

“…We have shown that FMDV replication is inhibited by prior treatment of cells with interferon type I (IFN-␣/␤), II, or III (6)(7)(8). Based on this information, we constructed Ad5 vectors containing porcine type I IFN genes (Ad5-poIFN-␣/␤) and demonstrated that swine inoculated with Ad5-poIFN-␣/␤ are protected from challenge with FMDV A24 Cruzeiro as early as 1 day after Ad5-poIFN-␣/␤ administration (4,9,10). Protection can last for 3 to 5 days (4).…”