Evolution and antiviral activity of a human protein of retroviral origin.

Endogenous retroviruses are abundant components of mammalian genomes descended from ancient germline infections. In several mammals, the envelope proteins encoded by these elements protect against exogenous viruses, but this activity has not been documented with endogenously expressed envelopes in humans. We report that the human genome harbors a large pool of envelope-derived sequences with the potential to restrict retroviral infection. To test this, we characterized an envelope-derived protein, Suppressyn. We found that Suppressyn is expressed in human preimplantation embryos and developing placenta using its ancestral retroviral promoter. Cell culture assays showed that Suppressyn, and its hominoid orthologs, could restrict infection by extant mammalian type D retroviruses. Our data support a generalizable model of retroviral envelope co-option for host immunity and genome defense.

APOBEC3A regulates transcription from interferon-stimulated response elements.

APOBEC3A (A3A) is a cytidine deaminase that inactivates a variety of viruses through introduction of lethal mutations to the viral genome. Additionally, A3A can suppress HIV-1 transcription in a deaminase-independent manner by binding to the long terminal repeat of proviral HIV-1. However, it is unknown whether A3A targets additional host genomic loci for repression. In this study, we found that A3A suppresses gene expression by binding TTTC doublets that are in close proximity to each other. However, one TTTC motif is sufficient for A3A binding. Because TTTC doublets are present in interferon (IFN)-stimulated response elements (ISRE), we hypothesized that A3A may impact IFN-stimulated gene (ISG) expression. After scanning the human genome for TTTC doublet occurrences, we discovered that these motifs are enriched in the proximal promoters of genes associated with antiviral responses and type I IFN (IFN-I) signaling. As a proof of principle, we examined whether A3A can impact ISG15 expression. We found that A3A binding to the ISRE inhibits phosphorylated STAT-1 binding and suppresses ISG15 induction in response to IFN-I treatment. Consistent with these data, our RNA-sequencing analyses indicate that A3A loss results in increased IFN-I­dependent induction of several ISGs. This study revealed that A3A plays an unexpected role in ISG regulation and suggests that A3A contributes to a negative feedback loop during IFN signaling.

Parental Responses to Transgender and Gender Nonconforming Youth: Associations with Parent Support, Parental Abuse, and Youths' Psychological Adjustment.

The purpose of this study was to examine parental responses to transgender and gender nonconforming [TGNC] youths' gender identities and explore associations of parent support with parental abuse, depressive symptoms, and LGBT-identity disclosure stress. TGNC youth (N = 129), ages 15-21 (M = 18.00, SD = 1.74), completed surveys (2011-2012); experiences of transfeminine (TF; n = 58) and transmasculine (TM; n = 71) youth were analyzed separately. Among mothers of TF youth, 42.0% of initial and 45.3% of current responses were positive; among fathers, 30.0% of initial and 36.0% of current responses were positive. Among mothers of TM youth, 26.0% of initial and 53.3% of current responses were positive; among fathers, 24.0% of initial and 44.6% of current responses were positive. Among TM youth, higher levels of parental support were associated with more positive responses from mothers and fathers. Among both TF and TM youth, greater parent support was associated with less parental abuse, depressive symptoms, and LGBTQ-identity disclosure stress. Parental responses to youths' gender identities became more positive with time for TF youth; however, approximately 50% of all TGNC youth continued to experience minority stress related to parent rejection. Limitations and implications for practice and research are discussed.

Co-option of endogenous viral sequences for host cell function.

Eukaryotic genomes are littered with sequences of diverse viral origins, termed endogenous viral elements (EVEs). Here we used examples primarily drawn from mammalian endogenous retroviruses to document how the influx of EVEs has provided a source of prefabricated coding and regulatory sequences that were formerly utilized for viral infection and replication, but have been occasionally repurposed for cellular function. While EVE co-option has benefited a variety of host biological functions, there appears to be a disproportionate contribution to immunity and antiviral defense. The mammalian embryo and placenta offer opportunistic routes of viral transmission to the next host generation and as such they represent hotbeds for EVE cooption. Based on these observations, we propose that EVE cooption is initially driven as a mean to mitigate conflicts between host and viruses, which in turn acts as a stepping-stone toward the evolution of cellular innovations serving host physiology and development.

Domestic harm and neglect among lesbian, gay, and bisexual older adults.

This study examined harm, hurt, and neglect by caregivers as well as self-neglect and physical and mental health status among 113 lesbian, gay, and bisexual (LGB) older adults aged 60-88 years, who attended community-based social and recreation programs or groups in the United States. Reporting on their experiences with caregivers, 22.1% of the participants experienced at least one type of harm, including physical, emotional, verbal, sexual, financial, and neglectful; additionally, 25.7% of the participants reported they knew LGB older adults who experienced at least one type of harm from his or her caregiver. With regard to self-neglect, 62.8% reported experiencing it; those indicating positive psychological health reported fewer experiences with self-neglect.