Pseudorabies Virus (PrV; also designated as Suid Alphaherpesvirus 1 (SuHV-1) or Aujeszky's Disease Virus (ADV)) is the causative agent of Aujeszky's disease of pigs. Due to its broad host range, PrV can infect numerous mammals with infection invariably leading to death. Only pigs can survive a productive PrV infection dependent on the age of the animal and the virulence of the virus and pigs are therefore considered as the natural host of PrV. Higher primates including humans and equids are resistant against infection (Mettenleiter, 2008).
PrV is grouped into the subfamily Alphaherpesvirinae of the family Herpesviridae which comprises also the human pathogens Herpes simplex virus 1 and 2, the causative agents of Herpes labialis (cold sores) and genitalis, and varicella-zoster virus (Chickenpox/Shingles), as well as important animal pathogens including the virus causing bovine infectious rhinotracheitis and pustular vulvovaginitis (bovine herpesvirus 1, BoHV-1), infectious laryngotracheitis of poultry (ILTV) or Marek's disease of poultry (MDV) (Roizman & Pellet, 2001).
Due to its fast lytic spread and broad host range, absence of pathogenicity for humans and the availability of the natural host, the pig, as experimental animal PrV is an excellent model to study the molecular mechanisms of herpesvirus infection in vitro and in vivo.
Fig. 1: Structure of a herpesvirus particle (PrV).
All herpesvirus particles (= virions) are morphologically identical comprising four different substructures (Fig. 1). The inner core contains the linear double-stranded DNA genome, which in PrV encompasses ca. 143.000 base pairs. The genome is enclosed in an icosahedral capsid, which together form the nucleocapsid. A proteinaceous tegument, corresponding to the matrix in RNA viruses, surrounds the nucleocapsid. The envelope is derived from intracytoplasmic membranes and contains virally encoded, mostly glycosylated proteins (= glycoproteins).
Fig. 2: Replication cycle of herpesviruses.
PrV is amongst the functionally and structurally best-characterized herpesviruses. Figure 2 schematically depicts the herpesvirus infection cycle. We are especially interested in stages of virus entry (1-2), nuclear egress of mature nucleocapsids (9-11), as well as secondary envelopment in the cytoplasm (11-13). As neurotropic herpesvirus, PrV is also able to replicate and spread in neurons. The molecular mechanisms of this process are also subject of intensive investigations. In addition, function of specific viral proteins is analyzed in the animal, mainly in mouse and pig.