Actinobacillus pleuropneumoniae Possesses an Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus

Abstract

Pigs are often colonized by more than one bacterial and/or viral species during respiratory tract infections. This phenomenon is known as the porcine respiratory disease complex (PRDC). Actinobacillus pleuropneumoniae (App) and porcine reproductive and respiratory syndrome virus (PRRSV) are pathogens that are frequently involved in PRDC. The main objective of this project was to study the in vitro interactions between these two pathogens and the host cells in the context of mixed infections. To fulfill this objective, PRRSV permissive cell lines such as MARC-145, SJPL, and porcine alveolar macrophages (PAM) were used. A pre-infection with PRRSV was performed at 0.5 multiplicity of infection (MOI) followed by an infection with App at 10 MOI. Bacterial adherence and cell death were compared. Results showed that PRRSV pre-infection did not affect bacterial adherence to the cells. PRRSV and App co-infection produced an additive cytotoxicity effect. Interestingly, a pre-infection of SJPL and PAM cells with App blocked completely PRRSV infection. Incubation of SJPL and PAM cells with an App cell-free culture supernatant is also sufficient to significantly block PRRSV infection. This antiviral activity is not due to LPS but rather by small molecular weight, heat-resistant App metabolites (<1 kDa). The antiviral activity was also observed in SJPL cells infected with swine influenza virus but to a much lower extent compared to PRRSV. More importantly, the PRRSV antiviral activity of App was also seen with PAM, the cells targeted by the virus in vivo during infection in pigs. The antiviral activity might be due, at least in part, to the production of interferon γ. The use of in vitro experimental models to study viral and bacterial co-infections will lead to a better understanding of the interactions between pathogens and their host cells, and could allow the development of novel prophylactic and therapeutic tools.

Update onActinobacillus pleuropneumoniae-knowledge, gaps and challenges

“…More recent co‐infection studies with a mild virulent PRRSV strain followed by a mild virulent App strain resulted in histological lung lesions, while this was not the case in monoinfected pigs (van Dixhoorn et al., ). On the other hand, in an in vitro model, App appeared to induce cell cycle arrest in the G2/M‐phase and inhibit PRRSV replication (Ferreira Barbosa, Labrie, Beaudry, Gagnon, & Jacques, ) resulting in an antiviral activity (Lévesque et al., ). It cannot be excluded that the order and interval between both infections is decisive for the final outcome of co‐infection.…”

Impact of Actinobacillus pleuropneumoniae biofilm mode of growth on the lipid A structures and stimulation of immune cells

“…cDNA was amplified using the SsoFast™ EvaGreen_Supermix kit (Bio-rad, Hercules, CA, USA). The primers used for amplification [32][33][34] are presented in Table 1.…”

Actinobacillus pleuropneumoniae induces SJPL cell cycle arrest in G2/M-phase and inhibits porcine reproductive and respiratory syndrome virus replication

“…This antiviral activity is not induced by A. pleuropneumoniae lipopolysaccharides or by peptidoglycan fragments (i.e. NOD1 and NOD2 ligands) [7].…”

“…We recently reported that A. pleuropneumoniae culture supernatant has an antiviral activity against PRRSV in vitro in SJPL infected cells and in porcine alveolar macrophages [7]. This antiviral activity is not induced by A. pleuropneumoniae lipopolysaccharides or by peptidoglycan fragments (i.e.…”

“…In vitro investigations can provide insights for understanding coinfections. Our laboratory recently developed a model to study co-infections by A. pleuropneumoniae and PRRSV using SJPL cells [7].…”