Molecular evolution of primate immunodeficiency viruses and hepatitis delta virus

Primate immunodeficiency viruses, or lentiviruses (HIV-1, HIV-2, and SIV), and hepatitis delta virus (HDV) are RNA viruses characterized by rapid evolution. Infection by primate immunodeficiency viruses usually results in the development of acquired immunodeficiency syndrome (AIDS) in humans and AIDS-like illnesses in Asian macaques. Similarly, hepatitis delta virus infection causes hepatitis and liver cancer in humans. These viruses are heterogeneous within an infected patient and among individuals. Substitution rates in the virus genomes are high and vary in different lineages and among sites. Methods of phylogenetic analysis were applied to study the evolution of primate lentiviruses and the hepatitis delta virus. The following results have been obtained: (1) The substitution rate varies among sites of primate lentivirus genes according to the two parameter gamma distribution, with the shape parameter $\alpha$ being close to 1. (2) Primate immunodeficiency viruses fall into species-specific lineages. Therefore, viral transmissions across primate species are not as frequent as suggested by previous authors. (3) Primate lentiviruses have acquired or lost their pathogenicity several times in the course of evolution. (4) Evidence was provided for multiple infections of a North American patient by distinct HIV-1 strains of the B subtype. (5) Computer simulations indicate that the probability of committing an error in testing HIV transmission depends on the number of virus sequences and their length, the divergence times among sequences, and the model of nucleotide substitution. (6) For future investigations of HIV-1 transmissions, using longer virus sequences and avoiding the use of distant outgroups is recommended. (7) Hepatitis delta virus strains are usually related according to the geographic region of isolation. (8) Evolution of HDV is characterized by the rate of synonymous substitution being lower than the nonsynonymous substitution rate and the rate of evolution of the noncoding region. (9) There is a strong preference for G and C nucleotides at the third codon positions of the HDV coding region. ^

Team: Bee Me. A formulative evaluation of a negative eating attitudes and behaviors primary prevention curriculum targeted at 5 th grade elementary school girls

Objective. To evaluate a school-based intervention aimed at the primary prevention of negative eating attitudes and behaviors among preadolescent girls, and to revise curriculum lessons based on quantitative and qualitative findings. ^ Intervention Design. A formative evaluation was conducted on four Team: Bee Me curriculum lessons at a Houston elementary school. Evaluation focused on program satisfaction and short-term effect on knowledge and eating attitudes and behaviors. ^ Results. Sixteen girls participated in the five-day project. Statistically significant improvements in overall knowledge were observed (p<0.05), however only modest changes were observed in eating attitudes and behaviors. Program satisfaction was high among student participants and the teacher who implemented it. Insight for future modifications to this program and for similar interventions was provided by the students and teacher. ^ Conclusions. This program led to positive trends in outcome variables; however longer and more intensive testing of this program is needed to better evaluate its effectiveness.^

Spatial distribution of orofacial cleft birth defects and uranium-radium concentrations in tap water in Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala Counties, Texas

Background Past and recent evidence shows that radionuclides in drinking water may be a public health concern. Developmental thresholds for birth defects with respect to chronic low level domestic radiation exposures, such as through drinking water, have not been definitely recognized, and there is a strong need to address this deficiency in information. In this study we examined the geographic distribution of orofacial cleft birth defects in and around uranium mining district Counties in South Texas (Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala), from 1999 to 2007. The probable association of cleft birth defect rates by ZIP codes classified according to uranium and radium concentrations in drinking water supplies was evaluated. Similar associations between orofacial cleft birth defects and radium/radon in drinking water were reported earlier by Cech and co-investigators in another of the Gulf Coast region (Harris County, Texas).50, 55 Since substantial uranium mining activity existed and still exists in South Texas, contamination of drinking water sources with radiation and its relation to birth defects is a ground for concern. ^ Methods Residential addresses of orofacial cleft birth defect cases, as well as live births within the twenty Counties during 1999-2007 were geocoded and mapped. Prevalence rates were calculated by ZIP codes and were mapped accordingly. Locations of drinking water supplies were also geocoded and mapped. ZIP codes were stratified as having high combined uranium (≥30μg/L) vs. low combined uranium (<30μg/L). Likewise, ZIP codes having the uranium isotope, Ra-226 in drinking water, were also stratified as having elevated radium (≥3 pCi/L) vs. low radium (<3 pCi/L). A linear regression was performed using STATA® generalized linear model (GLM) program to evaluate the probable association between cleft birth defect rates by ZIP codes and concentration of uranium and radium via domestic water supply. These rates were further adjusted for potentially confounding variables such as maternal age, education, occupation, and ethnicity. ^ Results This study showed higher rates of cleft births in ZIP codes classified as having high combined uranium versus ZIP codes having low combined uranium. The model was further improved by adding radium stratified as explained above. Adjustment for maternal age and ethnicity did not substantially affect the statistical significance of uranium or radium concentrations in household water supplies. ^ Conclusion Although this study lacks individual exposure levels, the findings suggest a significant association between elevated uranium and radium concentrations in tap water and high orofacial birth defect rates by ZIP codes. Future case-control studies that can measure individual exposure levels and adjust for contending risk factors could result in a better understanding of the exposure-disease association.^

Structural conservations and diversities of dsRNA viruses: Structural studies of the cytoplasmic polyhedrosis virus by electron cryomicroscopy and 3D reconstruction

The Reoviridae virus family is a group of economically and pathologically important viruses that have either single-, double-, or triple-shelled protein layers enclosing a segmented double stranded RNA genome. Each virus particle in this family has its own viral RNA dependent RNA polymerase and the enzymatic activities necessary for the mature RNA synthesis. Based on the structure of the inner most cores of the viruses, the Reoviridae viruses can be divided into two major groups. One group of viruses has a smooth surfaced inner core, surrounded by complete outer shells of one or two protein layers. The other group has an inner core decorated with turrets on the five-fold vertices, and could either completely lack or have incomplete outer protein layers. The structural difference is one of the determinant factors for their biological differences during the infection. ^ Cytoplasmic polyhedrosis virus (CPV) is a single-shelled, turreted virus and the structurally simplest member in Reoviridae. It causes specific chronic infections in the insect gut epithelial cells. Due to its wide range of insect hosts, CPV has been engineered as a potential insecticide for use in fruit and vegetable farming. Its unique structural simplicity, unparalleled capsid stability and ease of purification make CPV an ideal model system for studying the structural basis of dsRNA virus assembly at the highest possible resolution by electron cryomicroscopy (cryoEM) and three-dimensional (3D) reconstruction. ^ In this thesis work, I determined the first 3D structure of CPV capsids using 100 kV cryoEM. At an effective resolution of 17 Å, the full capsid reveals a 600-Å diameter, T = 1 icosahedral shell decorated with A and B spikes at the 5-fold vertices. The internal space of the empty CPV is unoccupied except for 12 mushroom-shaped densities that are attributed to the transcriptional enzyme complexes. The inside of the full capsid is packed with icosahedrally-ordered viral genomic RNA. The interactions of viral RNA with the transcriptional enzyme complexes and other capsid proteins suggest a mechanism for RNA transcription and subsequent release. ^ Second, the interactions between the turret proteins (TPs) and the major capsid shell protein (CSPs) have been identified through 3D structural comparisons of the intact CPV capsids with the spikeless CPV capsids, which were generated by chemical treatments. The differential effects of these chemical treatment experiments also indicated that CPV has a significantly stronger structural integrity than other dsRNA viruses, such as the orthoreovirus subcores, which are normally enclosed within outer protein shells. ^ Finally, we have reconstructed the intact CPV to an unprecendented 8 Å resolution from several thousand of 400kV cryoEM images. The 8 Å structure reveals interactions among the 120 molecules of each of the capsid shell protein (CSP), the large protrusion protein (LPP), and 60 molecules of the turret protein (TP). A total of 1980 α-helices and 720 β-sheets have been identified in these capsid proteins. The CSP structure is largely conserved, with the majority of the secondary structures homologous to those observed in the x-ray structures of corresponding proteins of other reoviruses, such as orthoreovirus and bluetongue virus. The three domains of TP are well positioned to play multifunctional roles during viral transcription. The completely non-equivalent interactions between LPP and CSP and those between the anchoring domain of TP and CSP account for the unparalleled stability of this structurally simplest member of the Reoviridae. ^