The Evolution of the Role of U.S. School Nurses in Adolescent Mental Health at the Individual, Community, and Systems Level: An Integrative Review.

School nurses are crucial to addressing adolescent mental health, yet evidence concerning their evolving role has not been synthesized to understand interventions across levels of practice (i.e., individual, community, systems). We conducted an integrative review of school nurse roles in mental health in the U.S. related to depressive symptoms, anxiety, and stress. Only 18 articles were identified, published from 1970 to 2019, and primarily described school nurses practicing interventions at the individual level, yet it was unclear whether they were always evidence-based. Although mental health concerns have increased over the years, the dearth of rigorous studies made it difficult to determine the impact of school nurse interventions on student mental health outcomes and school nurses continue to feel unprepared and under supported in this area. More research is needed to establish best practices and systems to support school nursing practice in addressing mental health at all levels of practice.

A Mixed Methods Exploration of Texas School Nurses' Involvement in Addressing Substance Use and Sexual/Reproductive Health Among Students in Alternative High Schools.

Students in alternative high schools (AHSs) have higher levels of substance use and risky sexual behaviors than students in traditional high schools. In this mixed methods study, we examine school nurses' efforts in Texas AHSs to address substance use and sexual/reproductive health. The nurses addressed substance use and sexual reproductive health mostly at the individual level, after students initiated risky behaviors. Nurses' efforts were influenced by district, school, and community factors (e.g., understaffing, outdated programs that weren't evidence-based or tailored to AHS students' behaviors, and family involvement). Usually, nurses were not practicing to their full scope as outlined by the National Association of School Nurses Framework. Substance use was a common reason for AHS placement and could contribute to the school-to-prison pipeline, and AHSs did not always have Narcan on campus to address drug overdoses. Our findings suggest implications for providing equitable health services to this underserved, understudied student population.

Effects of COVID-19 on School Nurse Mental Health Intervention Practices.

Mental health issues have been exacerbated by COVID-19; therefore we examined how the school nurses' role in addressing mental health changed during the pandemic. We administered a nationwide survey in 2021, guided by the Framework for the 21st Century School Nurse, and analyzed self-reported changes in mental health interventions by school nurses. Most mental health practice changes after the start of the pandemic occurred in the care coordination (52.8%) and community/public health (45.8%) principles. An overall decrease in students visiting the school nurse's office (39.4%) was seen, yet the frequency of students visiting with mental health concerns had increased (49.7%). Open-ended responses indicated that school nurse roles changed due to COVID-19 protocols, including decreased access to students and changes in mental health resources. These insights into the role of school nurses in addressing student mental health during public health disasters have important implications for future disaster preparedness efforts.

Challenges Facing Public Health Nursing Faculty in the United States: COVID-19 as a Catalyst for Change.

We present an analysis of challenges facing public health nursing faculty members (PHNF) in the United States and their broader societal implications. The COVID-19 pandemic has exacerbated these challenges, making them untenable. Current academic structures-influenced by the broader sociopolitical climate-are problematic for PHNF: they disincentivize PHNF from researching social determinants of health and public health systems, teaching systems-level content that may be deemed "controversial" and that is not included on licensure exams, and engaging in service through advocacy and community partnerships. The fault lines within health care, public health systems, and higher education indicate that it is time to reevaluate how to incentivize socially just and equitable outcomes. Toward this goal, we propose that collective action and systemic change, including the perspectives of PHNF, is needed to better realize our shared goals. The analysis serves as a catalyst for conversations about academic structures, health care systems, the role of public health, and the kind of society we envision for ourselves and future generations. (Am J Public Health. 2022;112(S3):S314-S320. https://doi.org/10.2105/AJPH.2022.306819).

Correlates of mental health problems among students in Texas alternative high schools and school-level efforts to address mental health.

Students in alternative high schools (AHSs) are an understudied population who experience disproportionate levels of risk factors that contribute to mental health problems. Using logistic regression, we explored associations between mental health problems and risk and protective factors among students in Texas AHSs (n = 515; mean age 17.1 years; 51% female, 78% youth of color, 64% eligible for free/reduced lunch). Principals (n = 14) and lead health educators (n = 14) reported on school-level efforts to address mental health. Students reported, on average, 1.55 of 4 mental health problems in the past year. Logistic regression indicated that greater number of adverse childhood experiences, lower self-esteem, female gender, and sleep disruption (getting <8 h of sleep per night) were common contributors to symptoms of depression, anxiety, suicidal ideation, and PTSD with models showing medium-to-large effects (AUC: 0.73-0.81). We assessed school-level efforts to address mental health using descriptive statistics. At the school level, most (>50%) principals reported having policies and services to support student mental health, with the exception of having mental health/social services staff represented on school health councils (36%) and having Gay-Straight Alliances (21%). Most lead health educators (86%) reported educating AHS students about mental health, and many (57%) reported receiving professional development in mental health. Future research with a larger number of schools is needed to analyze whether school policies are statistically associated with student-level mental health outcomes. Such multi-level research can inform policies and practices for AHS student mental health.

School-Level Efforts to Address Sexual Health and Risky Sexual Behavior Among Students in Texas Alternative High Schools.

We compared sexual/reproductive health services and sexuality education topics provided in Texas alternative high schools (AHSs) with the prevalence of sexual risk behaviors among students in AHS. Using cross-sectional data from convenience samples of 14 principals, 14 lead health educators, and 515 students, we calculated descriptive statistics for 20 services and 15 sexuality education topics provided by AHSs and seven sexual risk behaviors among students in AHS. AHSs provided few sexual/reproductive health services and limited educational content, despite high levels of sexual risk taking among students. For example, no AHSs taught students about proper condom use, yet 84% of students have had sex. Findings provide preliminary evidence of unmet needs for school-based sexual/reproductive health services and comprehensive sexuality education in AHS settings. Future investigation with larger, representative samples is needed to assess the provision of sexual/reproductive health services and sexuality education in AHSs and monitor sexual risk behaviors in the AHS population.

School Nurse Staffing in Texas Alternative High Schools: A Mixed Methods Exploration.

School nurses represent cost-effective investments in students' health and educational success. Alternative high schools (AHSs) serve an understudied population of youth who are at risk for school dropout and face numerous social inequities, heightening their risk for poor health outcomes. In this two-phase explanatory sequential mixed methods study, we examined school nurse staffing in Texas AHSs. Findings suggest Texas AHSs face understaffing for familiar reasons common across districts (e.g., lack of funding), but also reveal potential deeper inequities. Quantitative findings indicate 71% of Texas AHSs have some form of nursing support, most often an on-call or part-time nurse. Qualitative findings support and enrich this finding with insights into the negative consequences of not having a full-time nurse, indiscriminate approaches to staffing AHSs, and how AHSs can be the only school in the district without a full-time nurse. Altogether, our findings reveal opportunities to better support AHSs with adequate nursing support.

Correction: IFI16 Restricts HSV-1 Replication by Accumulating on the HSV-1 Genome, Repressing HSV-1 Gene Expression, and Directly or Indirectly Modulating Histone Modifications.

[This corrects the article DOI: 10.1371/journal.ppat.1004503.].

An Integrative Review: Understanding Parental Use of Social Media to Influence Infant and Child Health.

OBJECTIVES: Parents of young children have unique informational needs and it has been demonstrated that information-seeking behaviors influence health outcomes. Due to social media's popularity, understanding parents' use of social media may assist in disseminating accurate parenting information and in developing targeted interventions. Thus, we aimed to identify and describe the existing literature of parental use of social media for parenting in the U.S. METHODS: After searching nine databases with two separate Boolean phrases, identified articles were reviewed. Inclusion and exclusion criteria were applied, resulting in 12 articles published between January 2004 and May 2018 that related to parental use of social media for parenting or infant health in the U.S. Data from relevant articles were then extracted and analyzed. RESULTS: Facebook was the most frequent social media format. Parental utilization of social media varied by race/ethnicity and region. Studies primarily focused on women and a range of article topics were identified, the most common being infant feeding practices. Finally, two themes emerged: (1) parental support via social media and (2) effectiveness of using social media for health communication targeting parents. CONCLUSIONS FOR PRACTICE: Social media provided support for parents and was effective for communicating health information; thus, public health organizations should include social media in their efforts to promote infant and child health. More research is needed to further identify demographic differences in social media use among parents.

Using polytomous latent class analysis to compare patterns of substance use and co-occurring health-risk behaviors between students in alternative and mainstream high schools.

INTRODUCTION: Alternative high school (AHS) students, an understudied and underserved population, experience educational, social, and health disparities relative to students in mainstream high schools. Disparities in single types of substance use are particularly high, yet no known studies have compared patterns of substance use or relationships between these patterns and other health-risk behaviors between AHS and mainstream high schools. METHODS: Using data from the Texas Alternative School Health Survey (n = 515; mean age 17.1 years, 49% male, 59% Hispanic, 23% White, 15% Black) and the Texas Youth Risk Behavior Survey (n = 2,113; mean age 16 years, 47% male, 64% Hispanic, 22% White, 7% Black), we used latent class analyses to compare patterns of substance use in AHSs and mainstream high schools. We used latent class regression to examine relationships between patterns of substance use and involvement in other health-risk behaviors in each school setting. RESULTS: Students in AHSs and mainstream high schools had similar patterns of substance use, and youth in higher risk categories engaged in higher levels of other health-risk behaviors. A substantially greater proportion of AHS students, however, fell into the moderate and high use categories, in support of continuing disparities for AHS students. CONCLUSIONS: Additional support is needed in AHSs to address the prevalence of high-risk patterns of substance use and associated health-risk behaviors. For example, ongoing public health surveillance is needed in AHSs, just as is done in mainstream high schools, to monitor trends in substance use and impact of policies and interventions.

Teaching NICU Fellows How to Relay Difficult News Using a Simulation-Based Curriculum: Does Comfort Lead to Competence?

PROBLEM: Neonatal Intensive Care Unit (NICU) clinicians must frequently relay difficult news to patient families, and the need for formal training for NICU trainees to develop this skill has been established. Although previous studies have shown improved trainee self-efficacy and comfort in handling difficult conversations after formal communication training, it remains unclear whether these interventions lead to improved objectively assessed short-term and long-term performance. INTERVENTION: A simulation-based intervention emphasizing the SPIKES protocol for delivery of bad news was implemented for 15 fellows in the 3-year Baylor College of Medicine Neonatal-Perinatal Medicine fellowship program in the 2013-2014 academic year. Simulations involved video-recorded encounters between each fellow and a standardized parent (SP) involving communication of difficult news. Each fellow was evaluated before (preintervention), immediately after (postintervention), and 3-4 months after the intervention (follow-up) with an (a) evaluation of video-recorded sessions by two expert raters blinded to the timing of the encounter (blinded rater evaluation [BRE]), (b) Self-Assessment Questionnaire, (c) Content Test evaluating knowledge of taught concepts, and (d) SP evaluation (SPE). CONTEXT: The 1st- and 2nd/3rd-year fellows participated in the study at separate times in the academic year to accommodate their schedules. First-year fellows had had more prior communication training and less NICU clinical experience than the 2nd/3rd-year fellows at the time of their intervention. OUTCOME: Although all fellows displayed improved Self-Assessment and Content Test scores at postintervention with retention at the follow-up assessment, the BREs showed no statistically significant improvement in postintervention scores and showed a decline in follow-up scores. First-year fellows had higher BRE postintervention scores than the senior fellows. SPEs showed no difference in scores at all 3 assessment stages. LESSONS LEARNED: As previously described in the literature, trainee self-efficacy and knowledge may improve in the short term and long term with a simulation-based curriculum in communication of difficult news. However, these results may be inconsistent with those of objective evaluations by expert raters and standardized parents. The impact of the curriculum may be heightened if it reinforces previously learned skills, but the effect may wane over time if not reinforced frequently with additional formal training or in the clinical setting. The results of this study highlight the importance of objective assessments in evaluating the utility of a simulation-based communication curriculum and the need for longitudinal curricula to promote retention of the concepts and skills being taught.

Physical Activity Interventions to Decrease Substance Use in Youth: A Review of the Literature.

BACKGROUND: Adolescent substance use, a major problem in the United States, has a significant negative effect on both short- and long-term mental and physical health. Physical activity (PA) may offer potentially effective strategies to combat substance use in youth. Like substance use, PA behaviors developed during adolescence persist into adulthood, so adolescence may be an ideal period in which to implement PA interventions to prevent substance abuse. However, there are no known systematic literature reviews of PA-based interventions that target substance use in adolescence. OBJECTIVES: To review PA interventions for adolescents, including research designs, intervention characteristics, and measures of substance use. METHODS: Five databases were searched for articles published in English peer-reviewed journals. Search terms were related to the adolescent population, substance use, and PA interventions. RESULTS: 17 articles fit inclusion criteria. The results suggest that PA interventions may decrease substance use in teens. A majority of the interventions were delivered in high schools. Substance use measures/outcomes included intention or willingness to use, cessation, and actual use. Alcohol use was measured most, followed by marijuana and tobacco use. Although most of the studies utilized group sessions to deliver interventions, decreased substance use was also associated with one-time, multi-health consultations. Conclusions/Importance: School-based interventions targeting multiple health behaviors may offer a particularly effective and efficient way to decrease substance use in adolescents.

Full Coverage Sports Physicals: School Nurses' Untapped Role in Health Promotion Among Student Athletes.

Pre-participation physical exams (PPEs) hold great potential for addressing adolescents' health-risk behaviors. School nurses may be well positioned to assist with PPEs, yet little is known about their involvement. In this mixed methods study conducted in 2015, we collected data from school nurses in Texas (surveys, n = 208; key informant interviews, n = 10) to explore their roles and attitudes toward being involved in PPEs and addressing health-risk behaviors. Most respondents described minimal involvement in PPEs or were not involved to their full scope of practice. Most (69%) felt that school nurses are an untapped resource for addressing health-risk behaviors among student athletes. Interview participants felt that student athletes saw nurses as a "safe space" to talk about health-risk behaviors. Barriers included a lack of time, resources for follow-up, parental approval, and legal concerns. Study findings identify potential opportunities to support nurses' involvement in addressing health-risk behaviors among student athletes.

BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-ß Responses.

The innate immune system pattern recognition receptors (PRR) are the first line of host defenses recognizing the various pathogen- or danger-associated molecular patterns and eliciting defenses by regulating the production of pro-inflammatory cytokines such as IL-1ß, IL-18 or interferon ß (IFN-ß). NOD-like receptors (NLRs) and AIM2-like receptors (ALRs) are cytoplasmic inflammasome sensors of foreign molecules, including DNA. IFI16, a sequence-independent nuclear innate sensor ALR, recognizes episomal dsDNA genomes of herpes viruses such as KSHV, EBV, and HSV-1 in the infected cell nuclei, forms an inflammasome complex with ASC and procaspase1, and relocates into the cytoplasm leading into Caspase-1 and IL-1ß generation. IFI16 also induces IFN-ß during HSV-1 infection via the cytoplasmic STING-TBK1-IRF3 pathway. Thus far, whether IFI16 recognizes foreign DNA directly or utilizes other host protein(s) is unknown. Here, we demonstrate that BRCA1, a DNA damage repair sensor and transcription regulator, is in complex with IFI16 in the host cell nucleus, and their association increases in the presence of nuclear viral genomes during de novo KSHV, EBV and HSV-1 infection, and in latent KSHV or EBV infection, but not by DNA damage responses (DDR) induced by bleomycin and vaccinia virus cytoplasmic dsDNA. BRCA1 is a constituent of the triggered IFI16-inflammasome and is translocated into the cytoplasm after genome recognition along with the IFI16-inflammasome. The absence of BRCA1 abrogated IFI16-viral genome association, inflammasome assembly, IFI16 cytoplasmic localization, and Caspase-1 and IL-1ß production. The absence of BRCA1 also abolished the cytoplasmic IFI16-STING interaction, downstream IRF3 phosphorylation, nuclear translocation of pIRF3 and IFN-ß production during de novo KSHV and HSV-1 infection. These findings highlight that BRCA1 plays a hitherto unidentified innate immunomodulatory role by facilitating nuclear foreign DNA sensing by IFI16, subsequent assembly and cytoplasmic distribution of IFI16-inflammasomes leading into IL-1ß formation and the induction of IFN-ß via cytoplasmic signaling through IFI16-STING, TBK1 and IRF3.

Health Literacy in Adolescents With Sickle Cell Disease.

PURPOSE: To evaluate health literacy in a cohort of 75 adolescents with sickle cell disease (SCD). DESIGN AND METHODS: This cross-sectional, descriptive correlational study included assessment of demographic measures and appraisal of data resulting from completion of the REALM-Teen and Newest Vital Sign (NVS) instruments by 75 Black, non-Hispanic adolescents with SCD. Convenience sampling was utilized. Inclusion criteria were a diagnosis of one of the four primary genotypes of SCD and age 10-19years. RESULTS: Thirty-seven males and 38 females were recruited for the study. Their mean age was 14.7years (SD=2.2; range 8.1). Their grade level ranged from 4 to 12 (mean 8.7; SD=2.2). Scores on the REALM-Teen ranged from 12 to 66 (mean 53.7; SD=12.8). Scores on the NVS ranged from 0 to 6 (mean 2.37; SD=1.33). These health literacy scores were lower using both the REALM-Teen and the NVS instruments when compared to scores in all healthy adolescents and adults. Current grade level and health literacy scores showed a moderately high positive correlation (r=0.52, p<0.01). Health literacy scores were also significantly positively correlated with age (r=0.49, p<0.01) and income (r=0.37, p<0.01). CONCLUSIONS: Health literacy in adolescents with SCD is suboptimal. Future research should include identifying facilitators and barriers to health literacy levels in a larger cohort of adolescents with SCD. PRACTICE IMPLICATIONS: Health literacy is a potential facilitator of successful health outcomes for all adolescents. This study lays a solid foundation for future adolescent health literacy initiatives.

Reliability and Validity of the Child and Adolescent Behavior Assessment (CABA): A Brief Structured Scale.

Use of valid, affordable, accessible, and brief measures facilitates the assessment of mental health outcomes. The Child and Adolescent Behavior Assessment Scale, a brief, structured scale, assesses problem behavior through patient and/or informant report. The purpose of this paper is to illustrate the scale's psychometric properties. In the cross-sectional study presented, a large national sample of youth (aged 5-18) admitted for psychiatric treatment (N = 32,689) was examined. The two major domains of problem behavior assessed were Internalizing and Externalizing. Reliability was good to excellent with alpha levels ranging from 0.874 to 0.917. Additional items measured Risk Behavior (α = 0.648). Subscale total scores correlated well with the Brief Psychiatric Rating Scale for Children, 9-item version (BPRS-C-9). Exploratory and confirmatory factor analyses supported the three-factor, multidimensional model of problem behavior as satisfactory for child and adolescent use, although further research is required to refine some items for clarity and improved model fit.

Methods Matter: Tracking Health Disparities in Alternative High Schools.

Alternative high school (AHS) students are at-risk for school dropout and engage in high levels of health-risk behaviors that should be monitored over time. They are excluded from most public health surveillance efforts (e.g., Youth Risk Behavior Survey; YRBS), hindering our ability to monitor health disparities and allocate scarce resources to the areas of greatest need. Using active parental consent, we recruited 515 students from 14 AHSs in Texas to take a modified YRBS. We calculated three different participation rates, tracked participation by age of legal consent (≥18 and <18 years), and identified other considerations for obtaining quality data. Being required to use active consent resulted in a much lower cooperation rate among students <18 years (32%) versus those who were ≥18 years and could provide their own consent (57%). Because chronic truancy is prevalent in AHS students, cooperation rates may be more accurate than participation rates based off of enrollment or attendance. Requiring active consent and not having accurate participation rates may result in surveillance data that are of disparate quality. This threatens to mask the needs of AHS students and perpetuate disparities because we are likely missing the highest-risk students within a high-risk sample and cannot generalize findings.

Kaposi's sarcoma-associated herpesvirus induces Nrf2 activation in latently infected endothelial cells through SQSTM1 phosphorylation and interaction with polyubiquitinated Keap1.

UNLABELLED: Nuclear factor erythroid 2-related factor 2 (Nrf2), the cellular master regulator of the antioxidant response, dissociates from its inhibitor Keap1 when activated by stress signals and participates in the pathogenesis of viral infections and tumorigenesis. Early during de novo infection of endothelial cells, KSHV induces Nrf2 through an intricate mechanism involving reactive oxygen species (ROS) and prostaglandin E2 (PGE2). When we investigated the Nrf2 activity during latent KSHV infection, we observed increased nuclear serine-40-phosphorylated Nrf2 in human KS lesions compared to that in healthy tissues. Using KSHV long-term-infected endothelial cells (LTC) as a cellular model for KS, we demonstrated that KSHV infection induces Nrf2 constitutively by extending its half-life, increasing its phosphorylation by protein kinase Cζ (PKCζ) via the infection-induced cyclooxygenase-2 (COX-2)/PGE2 axis and inducing its nuclear localization. Nrf2 knockdown in LTC decreased expression of antioxidant genes and genes involved in KS pathogenesis such as the NAD(P)H quinone oxidase 1 (NQO1), gamma glutamylcysteine synthase heavy unit (γGCSH), the cysteine transporter (xCT), interleukin 6 (IL-6), and vascular endothelial growth factor A (VEGF-A) genes. Nrf2 activation was independent of oxidative stress but dependent on the autophagic protein sequestosome-1 (SQSTM1; p62). SQSTM1 levels were elevated in LTC, a consequence of protein accumulation due to decreased autophagy and Nrf2-mediated transcriptional activation. SQSTM1 was phosphorylated on serine-351 and -403, while Keap1 was polyubiquitinated with lysine-63-ubiquitin chains, modifications known to increase their mutual affinity and interaction, leading to Keap1 degradation and Nrf2 activation. The latent KSHV protein Fas-associated death domain-like interleukin-1ß-converting enzyme-inhibitory protein (vFLIP) increased SQSTM1 expression and activated Nrf2. Collectively, these results demonstrate that KSHV induces SQSTM1 to constitutively activate Nrf2, which is involved in the regulation of genes participating in KSHV oncogenesis. IMPORTANCE: The transcription factor Nrf2 is activated by stress signals, including viral infection, and responds by activating the transcription of cytoprotective genes. Recently, Nrf2 has been implicated in oncogenesis and was shown to be activated during de novo KSHV infection of endothelial cells through ROS-dependent pathways. The present study was undertaken to determine the mechanism of Nrf2 activation during prolonged latent infection of endothelial cells, using an endothelial cell line latently infected with KSHV. We show that Nrf2 activation was elevated in KSHV latently infected endothelial cells independently of oxidative stress but dependent on the autophagic protein sequestosome-1 (SQSTM1), which was involved in the degradation of the Nrf2 inhibitor Keap1. Furthermore, our results indicated that the KSHV latent protein vFLIP participates in Nrf2 activation. This study suggests that KSHV hijacks the host's autophagic protein SQSTM1 to induce Nrf2 activation, thereby manipulating the infected host gene regulation to promote KS pathogenesis.

The Nuclear DNA Sensor IFI16 Acts as a Restriction Factor for Human Papillomavirus Replication through Epigenetic Modifications of the Viral Promoters.

UNLABELLED: The human interferon-inducible IFI16 protein, an innate immune sensor of intracellular DNA, was recently demonstrated to act as a restriction factor for human cytomegalovirus (HCMV) and herpes simplex virus 1 (HSV-1) infection by inhibiting both viral-DNA replication and transcription. Through the use of two distinct cellular models, this study provides strong evidence in support of the notion that IFI16 can also restrict human papillomavirus 18 (HPV18) replication. In the first model, an immortalized keratinocyte cell line (NIKS) was used, in which the IFI16 protein was knocked down through the use of small interfering RNA (siRNA) technology and overexpressed following transduction with the adenovirus IFI16 (AdVIFI16) vector. The second model consisted of U2OS cells transfected by electroporation with HPV18 minicircles. In differentiated IFI16-silenced NIKS-HPV18 cells, viral-load values were significantly increased compared with differentiated control cells. Consistent with this, IFI16 overexpression severely impaired HPV18 replication in both NIKS and U2OS cells, thus confirming its antiviral restriction activity. In addition to the inhibition of viral replication, IFI16 was also able to reduce viral transcription, as demonstrated by viral-gene expression analysis in U2OS cells carrying episomal HPV18 minicircles and HeLa cells. We also provide evidence that IFI16 promotes the addition of heterochromatin marks and the reduction of euchromatin marks on viral chromatin at both early and late promoters, thus reducing both viral replication and transcription. Altogether, these results argue that IFI16 restricts chromatinized HPV DNA through epigenetic modifications and plays a broad surveillance role against viral DNA in the nucleus that is not restricted to herpesviruses. IMPORTANCE: Intrinsic immunity is mediated by cellular restriction factors that are constitutively expressed and active even before a pathogen enters the cell. The host nuclear factor IFI16 acts as a sensor of foreign DNA and an antiviral restriction factor, as recently demonstrated by our group for human cytomegalovirus (HCMV) and herpes simplex virus 1 (HSV-1). Here, we provide the first evidence that IFI16 inhibits HPV18 replication by repressing viral-gene expression and replication. This antiviral restriction activity was observed in immortalized keratinocytes transfected with the religated genomes and in U2OS cells transfected with HPV18 minicircles, suggesting that it is not cell type specific. We also show that IFI16 promotes the assembly of heterochromatin on HPV DNA. These changes in viral chromatin structure lead to the generation of a repressive state at both early and late HPV18 promoters, thus implicating the protein in the epigenetic regulation of HPV gene expression and replication.