Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans

Simian varicella virus (SVV), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV). Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP) resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox) in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation

Protective Mechanisms for Depression among Racial/Ethnic Minority Youth: Empirical Findings, Issues, and Recommendations

We (1) review empirical studies that report findings regarding putative protective mechanisms when exposed to risk of depression in African American and Hispanic adolescents; (2) identify key protective mechanisms for different risk contexts that garner empirical support; (3) synthesize the mechanisms identified as protective against depression among racial/ethnic minority adolescents; and (4) discuss improved methods for advancing understanding of resilience against depression in minority youth. The studies were selected from PsycINFO searches that met the following inclusion criteria: participants between 12 and 21 years of age, inclusions of racial/ethnic minority members, examining protection through an interaction with a risk factor, and outcome measures of depression, depressed mood, or depressive symptomatology. We found 39 eligible studies; 13 of which included multiple racial/ethnic groups. The following were supported as protective mechanisms, at least preliminarily, for at least one racial/ethnic group and in at least one risk context: employment, extracurricular activities, father–adolescent closeness, familism, maternal support, attending predominately minority schools, neighborhood composition, non-parent support, parental inductive reasoning, religiosity, self-esteem, social activities, and positive early teacher relationships. To investigate protective mechanisms more comprehensively and accurately across individual, social, and community levels of influence, we recommend incorporating multilevel modeling or multilevel growth curve analyses and large diverse samples

Mechanisms of drug combinations: Interaction and network perspectives

10.1038/nrd2683Nature Reviews Drug Discovery82111-12