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 ...