Rescue of the Epstein–Barr Virus BZLF1 Mutant, Z(S186A), Early Gene Activation Defect by the BRLF1 Gene Product

Expression of the Epstein-Barr virus (EBV) immediate-early protein, BZLF1 (Z), is sufficient to disrupt viral latency. Z transcriptionally activates the EBV early genes by binding to upstream Z-responsive elements (ZREs). Recently, a serine-to-alanine mutation of Z residue 186 (within the basic DNA binding domain) was shown to inhibit the ability of Z to induce lytic infection in latently infected cells, although the Z(S186A) mutant could still bind several known ZREs and activated an early EBV promoter (BMRF1) in transient reporter gene assays (Francis, A. L., Gradoville, L., and Miller, G. (1997). J. Virol. 71, 3054-3061). We now show that a specific deficiency in the ability to bind to ZRE elements in the immediate-early BRLF1 promoter may account for the inability of Z(S186A) to activate BRLF1 expression. Furthermore, we demonstrate that the ability of Z(S186A) to induce early BMRF1 and BHRF1 gene expression is rescued by cotransfection with a BRLF1 expression vector. However, the Z(S186A)/BRLF1 (R) combination cannot induce full lytic replication, suggesting that Z(S186A) may also be deficient in a replication-specific function. These results suggest that in the context of the intact viral genome, both Z and R expression are required for activation of early gene transcription in latently infected cells

Use of Protective Behavioral Strategies and Reduced Alcohol Risk: Examining the Moderating Effects of Mental Health, Gender and Race

Recent research indicates that protective behavioral strategies (PBS)—previously established as effective self-regulating tools for reducing alcohol risk among college students—may be especially useful for students with poor mental health, who are shown to be at heightened risk for alcohol-related harm. The current study examined the moderating influence of mental health (depression and anxiety severity), gender, and race (White, Asian) in the relationship between PBS use and alcohol-related negative consequences. Participants were 1,782 undergraduate students from two West Coast universities who reported past month incidence of heavy episodic drinking. Students reported on their drinking, experience of alcohol-related consequences, use of PBS, and depression and anxiety symptomatology. Overall, results demonstrated that among participants experiencing depression or anxiety, greater PBS utilization was associated with significantly lower levels of alcohol-related consequences, even after controlling for drinking and other predictors. However, findings also revealed important distinctions in the potential effectiveness of PBS by depression/anxiety severity and racial-gender subgroup, such that Asian men with poor mental health appeared to garner unique and substantial benefit (i.e., lesser consequences) from increased PBS use. Further, PBS were found to offer substantial protective benefit for White females, irrespective of mental health. This study points to the potential for targeted PBS-specific skills training and interventions to minimize alcohol-related risks faced by the growing subpopulation of college students experiencing psychological distress, and further highlights important race-gender differentials

Rescue of the Epstein–Barr Virus BZLF1 Mutant, Z(S186A), Early Gene Activation Defect by the BRLF1 Gene Product

Expression of the Epstein-Barr virus (EBV) immediate-early protein, BZLF1 (Z), is sufficient to disrupt viral latency. Z transcriptionally activates the EBV early genes by binding to upstream Z-responsive elements (ZREs). Recently, a serine-to-alanine mutation of Z residue 186 (within the basic DNA binding domain) was shown to inhibit the ability of Z to induce lytic infection in latently infected cells, although the Z(S186A) mutant could still bind several known ZREs and activated an early EBV promoter (BMRF1) in transient reporter gene assays (Francis, A. L., Gradoville, L., and Miller, G. (1997). J. Virol. 71, 3054-3061). We now show that a specific deficiency in the ability to bind to ZRE elements in the immediate-early BRLF1 promoter may account for the inability of Z(S186A) to activate BRLF1 expression. Furthermore, we demonstrate that the ability of Z(S186A) to induce early BMRF1 and BHRF1 gene expression is rescued by cotransfection with a BRLF1 expression vector. However, the Z(S186A)/BRLF1 (R) combination cannot induce full lytic replication, suggesting that Z(S186A) may also be deficient in a replication-specific function. These results suggest that in the context of the intact viral genome, both Z and R expression are required for activation of early gene transcription in latently infected cells

The bZip Dimerization Domain of the Epstein–Barr Virus BZLF1 (Z) Protein Mediates Lymphoid-Specific Negative Regulation

AbstractThe Epstein–Barr virus (EBV) immediate-early (IE) protein, BZLF1 (Z), initiates the switch from latent to lytic infection. Z transactivation of an early viral promoter, BMRF1, is relatively inefficient in lymphoid cells (compared with epithelial cells), unless the other EBV IE protein, BRLF1, is also present. Cellular proteins, including the p65 component of NF-κB, have been shown to interact directly with Zin vitrothrough the bZip dimerization domain and inhibit Z-induced transactivation. Here we precisely define a residue within the bZip dimerization domain of Z (amino acid 200) which is required for interactionin vitrowith the p65 component of NF-κB, but is not essential for Z homodimerization. In lymphoid cells, a Z mutant which has been altered at amino acid 200 (tyrosine to glutamic acid) transactivates both the early BMRF1 promoter and the immediate-early BZLF1 promoter (Zp) four- to fivefold better than wild-type Z. In contrast, mutation of amino acid 200 does not affect Z transactivator function in epithelial cells. The results suggest that Z function is specifically inhibited by a lymphoid-specific protein(s) through amino acid 200 in the bZip dimerization domain. Modulation of Z's activator function may help to regulate the stringency of viral latency in lymphocytes

Injunctive Peer Misperceptions and the Mediation of Self-Approval on Risk for Driving After Drinking Among College Students

Of the alcohol-related risks faced by college students, it is arguable that none presents a greater public health hazard than driving after drinking (DAD). The present study examined the extent to which students’ injunctive misperceptions toward DAD predicted the likelihood to engage in DAD and how this relation was mediated by self-approval of DAD. Participants were 2,848 college students (59.1% female, 64.6% Caucasian) from two U.S. West Coast universities who completed confidential web-based surveys assessing DAD beliefs and behaviors. Results revealed that respondents tended to overestimate their peers’ approval toward DAD. Moreover, the subgroups likely to engage in DAD—men, 21+ years of age, Greek affiliated students, Caucasians, students with a family history of alcohol abuse—were also more likely to misperceive (i.e., overestimate) their peers’ level of approval toward DAD. Using binary logistic regression analyses, self-approval of DAD emerged as an important statistical mediator in the relation between misperception of typical student approval toward DAD and engagement in DAD. Results point to the considerable role injunctive peer misperceptions may play in the pathways leading to drinking-driving risk. These findings provide preliminary support for DAD-specific social normative interventions, either complementing or supplementing existing alcohol interventions. By targeting high-risk student subgroups and communicating accurate drinking-driving norms, these proposed interventions have the potential to reduce self-approval and incidence of DAD

The Use of Protective Behavioral Strategies is Related to Reduced Risk in Heavy Drinking College Students with Poorer Mental and Physical Health

The present study examined the moderating role of health status (physical, mental, and social health) and the relationships between protective behavioral strategies utilized to reduce high-risk drinking (e.g., avoiding drinking games, setting consumption limits, or having a designated driver) and alcohol use and negative consequences in a sample of heavy drinking college students (N = 1,820). In this high risk sample, multiple regression analyses showed that stronger social health was related to increased drinking, while poorer physical, mental, and social health were related to increased alcohol negative consequences. Further, moderation effects revealed that increasing the use of protective behaviors was associated with significantly less drinking in those with stronger social health, as well as significantly lower numbers of negative consequences among participants with poorer physical and mental health. Implications for college counselors and medical personnel are discussed

The Longitudinal Relationships among Injunctive Norms and Hooking Up Attitudes and Behaviors in College Students

Limited research has explored the influence of perceived injunctive norms for distal (e.g., typical student) and proximal (e.g., close friend and parents) referents on hooking up. The current study examined the longitudinal relationships among perceived injunctive norms, personal approval and hooking up behavior, and the moderating effects of gender in a sample of heavy drinking college students. At Time 1, participants completed web-based assessments of personal approval of hooking up and perceptions of close friend, parent, and typical student approval. Three months later, participants reported on whether they had hooked up. The results of a path analysis indicated that greater perceived friend and parent approval predicted greater personal approval. Further, greater perceived approval by close friends and parents indirectly contributed to hooking up behavior as mediated by participants’ own approval. Multigroup analyses indicated that close friend injunctive norms were a stronger predictor of student approval for males, as compared to females. While previous research has often failed to find an association between perceived injunctive norms and hooking up, the current findings suggest that this may reflect the use of distal referents. The findings underscore that perceptions of close friend and family approval may be useful predictors of hooking up behavior

Social anxiety and drinking refusal self-efficacy moderate the relationship between drinking game participation and alcohol-related consequences

Background Participation in drinking games is associated with excessive drinking and alcohol risks. Despite the growing literature documenting the ubiquity and consequences of drinking games, limited research has examined the influence of psychosocial factors on the experience of negative consequences as the result of drinking game participation. Objectives The current event-level study examined the relationships among drinking game participation, social anxiety, drinking refusal self-efficacy (DRSE) and alcohol-related consequences in a sample of college students. Methods Participants (n =976) reported on their most recent drinking occasion in the past month in which they did not preparty. Results After controlling for sex, age, and typical drinking, higher levels of social anxiety, lower levels of DRSE, and playing drinking games predicted greater alcohol-related consequences. Moreover, two-way interactions (Social Anxiety × Drinking Games, DRSE × Drinking Games) demonstrated that social anxiety and DRSE each moderated the relationship between drinking game participation and alcohol-related consequences. Participation in drinking games resulted in more alcohol problems for students with high social anxiety, but not low social anxiety. Students with low DRSE experienced high levels of consequences regardless of whether they participated in drinking games; however, drinking game participation was associated with more consequences for students confident in their ability to resist drinking. Conclusion Findings highlight the important role that social anxiety and DRSE play in drinking game-related risk, and hence provide valuable implications for screening at-risk students and designing targeted harm reduction interventions that address social anxiety and drink refusal in the context of drinking games

An Examination of Prepartying and Drinking Game Playing During High School and Their Impact on Alcohol-Related Risk Upon Entrance into College

Prepartying and drinking game playing are associated with excessive alcohol consumption and alcohol-related negative consequences in college populations; however, research exploring the prevalence of these high risk drinking contexts among high school students, and how such engagement may impact both high school and subsequent college drinking risk, is lacking. The current study, which is the first study to assess prepartying during high school, examined how engaging in either prepartying or drinking game playing during high school was associated with risky high school drinking as well asalcohol use and consequences during the transitional first month of college. The study involved 477 first-year college students, the majority of whom were 18 years old (94%), female (66%), and Caucasian (59%). Prepartying was found to be highly prevalent in high school (45%). Further, students who prepartied or played drinking games during high school drank significantly more in high school than students who did not engage in these high risk activities. Finally, prepartying and game playing during high school were associated with greater collegiate alcohol consumption (controlling for high school drinking) and consequences (controlling for both high school and college drinking). This study establishes prepartying and drinking games as common high risk activities among both high school and incoming first-year college students, and addresses implications for prevention and targeted interventions

Family History of Alcohol Abuse Associated With Problematic Drinking Among College Students

Studies examining family history of alcohol abuse among college students are not only conflicting, but have suffered various limitations. The current report investigates family history of alcohol abuse (FH+) and its relationship with alcohol expectancies, consumption, and consequences. In the current study, 3753 student participants (35% FH+), completed online assessments. Compared to FH−same-sex peers, FH+ males and FH+ females endorsed greater overall positive expectancies, consumed more drinks per week, and experienced more alcohol-related negative consequences. Further, FH+ females evaluated the negative effects of alcohol to be substantially worse than FH− females. An ANCOVA, controlling for age, GPA, race, and alcohol expectancies, resulted in family history main effects on both drinking and consequences. An interaction also emerged between gender and family history, such that FH+ males were especially vulnerable to high levels of alcohol consumption. Results reveal the scope of FH+ individuals in the college environment and the increased risk for these students, particularly male FH+ students, suggesting a need for researchers and college health personnel to focus attention and resources on this issue