Porcine reproductive and respiratory syndrome virus entry into the porcine macrophage

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) emerged in the late 1980s and rapidly became one of the most significant viral pathogens in the swine industry. In vivo, the virus shows a very narrow cell tropism and targets specific subsets of porcine macrophages. The entry of PRRSV into its host cell is the first crucial step in infection and has been the focus of many fundamental studies. This review provides a comprehensive overview of the current knowledge on PRRSV entry into the porcine macrophage, covering virus binding, internalization and genome release, and integrates these findings into a general model of the entry process. IntroductionPorcine reproductive and respiratory syndrome (PRRS) severely affects swine populations worldwide. The aetiological agent, the PRRS virus (PRRSV), is an RNA virus that is classified within the family Arteriviridae, order Nidovirales (Cavanagh, 1997). PRRSV causes considerable production losses as infection with the virus can result in severe reproductive and respiratory disorders in pigs (Neumann et al., 2005). With the recent outbreaks of highly virulent variants of the virus in China (Li et al., 2007;Tian et al., 2007;Zhou et al., 2008), interest in PRRSV has increased greatly and the demand for safe and effective vaccines for PRRSV control is higher than ever.The PRRSV virion consists of a nucleocapsid, composed of a positive-strand RNA genome (±15 kb) and the nucleocapsid protein (N), which is surrounded by a lipid bilayer envelope Dea et al., 1995;Mardassi et al., 1994;Meulenberg et al., 1993;Spilman et al., 2009;Wensvoort et al., 1992). The viral envelope contains six structural proteins: the small envelope protein E, the membrane protein M and the N-glycosylated glycoproteins GP 2 (or GP 2a ), GP 3 , GP 4 and GP 5 . M, N and GP 5 are the major structural proteins of PRRSV, while E, GP 2 , GP 3 and GP 4 are minor virion components. The M and GP 5 proteins occur as disulfide-linked heterodimers in the envelope, while the minor structural proteins E, GP 2 , GP 3 and GP 4 appear to associate via non-covalent interactions (Mardassi et al., 1995(Mardassi et al., , 1996Meulenberg et al., 1993Meulenberg et al., , 1995van Nieuwstadt et al., 1996; Wissink et al., 2005;Wu et al., 2001). In addition, recent data suggest that interactions exist between major and minor envelope proteins (Das et al., 2010).Since the discovery of PRRSV, many studies have been performed to gain insight into the biology of this important pathogen. This review reflects on two decades of research on the initial steps of the PRRSV replication cycle, covering virus attachment, internalization and disassembly. A general model of PRRSV entry into the porcine macrophage is proposed and delineates where further research is necessary. PRRSV cell tropismLike other members of the family Arteriviridae, PRRSV has a very narrow cell tropism. In vivo, the virus shows a preference for cells of the monocyte/macrophage lineage and infects specific subsets of differentiated macrophages in lungs, lymphoid ...

A Single Amino Acid Deletion in the Matrix Protein of Porcine Reproductive and Respiratory Syndrome Virus Confers Resistance to a Polyclonal Swine Antibody with Broadly Neutralizing Activity

“…An alternative explanation can be based on the structure formed by the GP5-M heterodimer molecule and its interaction with the receptor on macrophages. Previous models identified the interaction between CD169 and GP5 as being responsible for the initial uptake and internalization of the virus, which is followed by uncoating via an interaction between GP2, -3, and -4 and CD163 (40). However, productive infection of CD169 knockout pigs with PRRSV has brought into question the role of GP5/M as a receptor-binding molecule (41).…”

Infection of porcine bone marrow-derived macrophages by porcine respiratory and reproductive syndrome virus impairs phagosomal maturation

“…The causative agent is the porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped positive-sense ssRNA virus of the genus Arterivirus. PRRSV targets cells of the monocyte-macrophage lineage, primarily alveolar and interstitial macrophages and dendritic cells in the lungs, and macrophages found in the spleen, lymph nodes, Peyer's patches, placenta and endometrium (Beyer et al, 2000;Duan et al, 1997a, b;Halbur et al, 1995;Lawson et al, 1997;Thanawongnuwech et al, 2000;Van Breedam et al, 2010). The targeting of professional phagocytes, in particular alveolar macrophages, by PRRSV leads to significant additional morbidity and mortality in part due to impairment of the ability of the alveolar macrophages to clear infections by invading concurrent and secondary pathogens in the lungs (Drew, 2000;enzymes (Fairn & Grinstein, 2012;Flannagan et al, 2012).…”

Porcine Reproductive and Respiratory Syndrome Virus Infection at the Time of Porcine Circovirus Type 2 Vaccination Has No Impact on Vaccine Efficacy

“…PRRSV primarily infects the monocyte/macrophage cell line (11) via CD163 scavenger receptor and heparin sulfate and sialoadhesin receptors (10,46), which are also involved in the primary defense of the innate immune system (9,21). It causes reproductive failure in pregnant sows and respiratory disease in pigs of all ages and is also associated with neonatal diarrhea (1,3,23,37).…”