THE GLYCOPROTEINS OF PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS AND THEIR ROLE IN INFECTION AND IMMUNITY

The porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen of swine and is known to cause abortion and infertility in pregnant sows and respiratory distress in piglets. PRRSV contains a major glycoprotein (GP5) and three minor glycoproteins (GP2a, GP3, and GP4) on the virion envelope, all of which are required for infectious virus production. To study their interactions amongst each other and with a cellular receptor for PRRSV, CD163, I cloned each of the viral glycoproteins and CD163 in various expression vectors. My studies have shown that while the GP2a, GP3, and GP4 are co-translationally glycosylated, the GP5 is post-translationally glycosylated. By using co-immunoprecipitation (co-IP) assays, strong interaction was demonstrated between GP4 and GP5 proteins, although weak interactions among the other envelope glycoproteins were also detected. Further, GP4 was found to mediate interactions leading to formation of multiprotein glycoprotein complex. My results also show that GP2a and GP4 proteins are the only two GPs that specifically interact with the CD163 molecule and that glycosylation of these GPs is required for efficient interaction. Based on these studies, I have developed an interactome map of the viral GPs and CD163 and have proposed a model of the viral glycoprotein complex and its interaction with CD163. Studies reported here also show that glycan addition at residue 184 (N184) of GP2a, and residues N42, N50, and N131 of GP3 is essential for recovery of infectious virus. Although single site glycosylation mutants of GP4 had no effect on infectious virus production, introduction of double mutations was lethal. The loss of glycan moieties of GP2a, GP3, and GP4 proteins had no effect on host neutralizing antibody production. Overall, I conclude that the PRRSV glycoproteins are co-translationally and post-translationally glycosylated, the GP4 protein is central to mediating interglycoprotein interactions, and along with GP2a, serves as the viral attachment protein that is responsible for interactions with the viral receptor, CD163. Further, glycosylation of GP2a, GP3, and GP4 proteins is required for infectious virus production, efficient interaction with CD163, but does not play any role in neutralizing antibody response in infected animals.

The Quality of Spousal Social Support as a Moderator of the Associations Between Child Maltreatment Severity and Adult Trauma Symptoms

Child maltreatment has been linked to a myriad of long-term difficulties, including trauma symptomatology. However, not all victims experience long-term distress. Thus, a burgeoning area of research focuses on factors that may impede or facilitate resiliency to the psychological correlates of child maltreatment. Specifically, the severity of the abusive acts may be associated with greater long-term difficulties. To date, however, with the exception of child sexual abuse, few studies have examined the severity of maltreatment as a risk factor in the development of trauma symptoms. In contrast, social support has been theorized to contribute to resiliency following abuse. However, to date, the majority of studies examining positive social support as a protective factor have relied on self-report measures of perceived social support, rather than observational measures of received social support. Moreover, no study to date has examined the role that negative social support (i.e, blaming, criticizing) may play in potentiating trauma symptoms among victims of child maltreatment. Because child maltreatment involves serious boundary violations by a trusted person, a marital relationship is an important domain in which to examine these constructs. That is, it may serve as an arena for the manifestation of psychological disturbances related to maltreatment. Thus, the present study examined whether observationally measured positive and negative spousal social support moderated the relationship between child maltreatment severity (i.e., sexual, physical, psychological abuse; neglect) and trauma symptomatology in women and men. Results indicated that the severity of each type of child maltreatment significantly predicted increased adult trauma symptomatology. Contrary to hypothesized outcomes, positive spousal social support did not predict decreased trauma symptomatology. However, negative spousal social support generally did predict increased trauma symptomatology. There were no consistent patterns of interactions between child maltreatment severity and either type of social support. Future directions for research will be discussed and clinical implications with regard to the intrapersonal and interpersonal functioning of child maltreatment victims will be highlighted.