Development and Assessment of a Prenatal Cytomegalovirus (CMV) Educational Survey: Implementation and Impact in a Metropolitan University-Based Clinic.

PURPOSE: Congenital CMV infection can result in serious sequelae in the newborn. The goal of this study was to assess pregnant women's knowledge and understanding of CMV infection during pregnancy and develop an educational tool about CMV infection to be utilized during prenatal care. MATERIALS AND METHODS: This is a prospective intervention study that assessed pregnant women's knowledge before and after receiving an educational handout about CMV infection in pregnancy and the perceived value of this education. Pre- and post-education questionnaires were utilized to assess knowledge. The pre-education questionnaire and CMV educational handout were given at the same clinic visit. The educational handout was given after the pre-education questionnaire had been completed. The post-education questionnaire was given at the next scheduled prenatal clinic appointment and included questions regarding the level of satisfaction with the education and the perceived value of the information. Pregnant women less than 34 weeks of gestation were eligible. RESULTS: A total of 263 women were enrolled, 263 completed the pre-CMV educational questionnaire and 215 women completed both questionnaires. Some women only partially completed the questionnaires and those partial responses have been included. Prior to education, 33% (85/261) of participants had heard of CMV. This increased to 75% (160/214) after education. Participants scored each of the recommended hygiene practices between 1 and 5 (5 is the most acceptable) and each recommended hygiene practice received an average score between 3.8 and 5. 74% (134/180) of participants reported increasing their hygienic practices after education. 96% (180/188) of participants indicated they were satisifed to have received the education. 98% (187/190) thought more women should receive this education during prenatal care. CONCLUSION: Pregnant women viewed education about CMV favorably and increased the frequency of recommended hygiene practices. Introducing an educational handout to routine prenatal care may be beneficial in increasing awareness of CMV infection in pregnancy.

HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP-dependent pathway in T cells.

To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I). To accomplish this, Nef binds to the cytoplasmic tails of both molecules and then, by mechanisms that are not well understood, disrupts the trafficking of each molecule in different ways. Specifically, Nef promotes CD4 internalization after it has been transported to the cell surface, whereas Nef uses the clathrin adaptor, AP-1, to disrupt normal transport of MHC-I from the TGN to the cell surface. Despite these differences in initial intracellular trafficking, we demonstrate that MHC-I and CD4 are ultimately found in the same Rab7(+) vesicles and are both targeted for degradation via the activity of the Nef-interacting protein, beta-COP. Moreover, we demonstrate that Nef contains two separable beta-COP binding sites. One site, an arginine (RXR) motif in the N-terminal alpha helical domain of Nef, is necessary for maximal MHC-I degradation. The second site, composed of a di-acidic motif located in the C-terminal loop domain of Nef, is needed for efficient CD4 degradation. The requirement for redundant motifs with distinct roles supports a model in which Nef exists in multiple conformational states that allow access to different motifs, depending upon which cellular target is bound by Nef.

A novel trafficking signal within the HLA-C cytoplasmic tail allows regulated expression upon differentiation of macrophages.

MHC class I molecules (MHC-I) present peptides to CTLs. In addition, HLA-C allotypes are recognized by killer cell Ig-like receptors (KIR) found on NK cells and effector CTLs. Compared with other classical MHC-I allotypes, HLA-C has low cell surface expression and an altered intracellular trafficking pattern. We present evidence that this results from effects of both the extracellular domain and the cytoplasmic tail. Notably, we demonstrate that the cytoplasmic tail contains a dihydrophobic (LI) internalization and lysosomal targeting signal that is partially attenuated by an aspartic acid residue (DXSLI). In addition, we provide evidence that this signal is specifically inhibited by hypophosphorylation of the adjacent serine residue upon macrophage differentiation and that this allows high HLA-C expression in this cell type. We propose that tightly regulated HLA-C surface expression facilitates immune surveillance and allows HLA-C to serve a specialized role in macrophages.