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Assessment of virus neutralization (VN) activity in 176 pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) identified one pig with broadly neutralizing activity. A Tyr-10 deletion in the matrix protein provided escape from broad neutralization without affecting homologous neutralizing activity. The role of the Tyr-10 deletion was confirmed through an infectious clone with a Tyr-10 deletion. The results demonstrate differences in the properties and specificities of VN responses elicited during PRRSV infection. P orcine reproductive and respiratory syndrome virus (PRRSV) causes respiratory disease in young pigs, reduced performance in growing pigs, and reproductive failure in gilts and sows (1). Generally, vaccination with modified live virus (MLV) or previous natural infection results in only homologous protection against closely related isolates (2). Under some circumstances, protection is expanded to include more genetically distant viruses (3). The paucity of heterologous protection is attributed to a number of factors, such as antigenic drift in B and T cell epitopes (4, 5) and glycan shielding of conserved epitopes (6).The enveloped virion surface contains at least six proteins. The major proteins, GP5 and M, encoded by open reading frames (ORFs) 5 and 6, respectively, form a disulfide-linked heterodimer (7). The minor surface glycoproteins, GP2, GP3, and GP4, encoded by ORFs 2, 3, and 4, respectively, form a noncovalent heterotrimer (8). Finally, there are two small nonglycosylated proteins, E and 5a, encoded by ORFs 2b and 5a, respectively (9-11). As summarized in Fig. S1 in the supplemental material, several previous studies have identified multiple neutralizing epitopes distributed among the major and minor surface proteins. For example, a PEPSCAN analysis of Lelystad virus (LV), a type 1 virus, identified a short peptide sequence in GP4 as the epitope linked with virus neutralization (VN) by a monoclonal antibody (MAb) prepared against purified virions (12) (epitope c in Fig. S1D in the supplemental material). The same region in GP4 was identified as a target for neutralizing antibodies derived from experimentally infected pigs (13). Fig. S1F in the supplemental material). A similar epitope is found in GP5 of a closely related arterivirus, lactate dehydrogenase-elevating virus (LDV) (18). In an effort to understand the role of envelope-associated proteins in the cross-neutralization of genetically distinct PRRSV isolates, Kim and Yoon (19) reacted neutralizing swine serum with a panel of chimeric viruses constructed of structural genes derived from neutralization-sensitive and neutralization-resistant viruses. When individual ORFs were replaced, the largest increase in VN resistance or susceptibility was obtained following the exchange of GP3 or GP5. The search for additional epitopes has become more complicated by a recent report describing nsp2 as a virus-associated protein (20).One explanation for the absence of agreement in the characterization of PRRSV neutralizing epit...

African swine fever is a highly contagious, often fatal disease of swine for which there is no vaccine or other curative treatment. The macrophage marker, CD163, is a putative receptor for African swine fever virus (ASFV). Pigs possessing a complete knockout of CD163 on macrophages were inoculated with Georgia 2007/1, a genotype 2 isolate. Knockout and wild type pen mates became infected and showed no differences in clinical signs, mortality, pathology or viremia. There was also no difference following in vitro infection of macrophages. The results do not rule out the possibility that other ASFV strains utilize CD163, but demonstrate that CD163 is not necessary for infection with the Georgia 2007/1 isolate. This work rules out a significant role for CD163 in ASFV infection and creates opportunities to focus on alternative receptors and entry mechanisms.

After infection of the porcine dam at about 90 days of gestation, porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta and begins to infect fetuses. Outcomes of include abortion, fetal death and respiratory disease in newborn piglets. CD163 is the receptor for the virus. In this study, CD163-positive fetuses, recovered between 109 days of gestation or 20 days after maternal infection, were completely protected from PRRSV in dams possessing a complete knockout of the CD163 receptor. The results demonstrate a practical means to eliminate PRRSV-associated reproductive disease, a major source of economic hardship to agriculture.