RESUMEN
Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential mechanistic link between acute HIV-1 infection, lymphoid tissue breakdown, and persistent immune dysfunction.
Asunto(s)
Infecciones por VIH/inmunología , VIH-1/inmunología , Interferón gamma/metabolismo , Intestinos/patología , Linfocitos/inmunología , Enfermedad Aguda , Antivirales/administración & dosificación , Apoptosis/efectos de los fármacos , Apoptosis/genética , Movimiento Celular , Células Cultivadas , Enfermedad Crónica , Estudios de Cohortes , Regulación de la Expresión Génica , Infecciones por VIH/tratamiento farmacológico , Humanos , Inmunidad Innata , Interferón gamma/genética , Intestinos/virología , Linfocitos/efectos de los fármacos , Linfocitos/virología , Factores de Tiempo , Resultado del Tratamiento , Carga Viral/efectos de los fármacos , Carga Viral/inmunologíaRESUMEN
Mycobacteriophages--viruses of mycobacterial hosts--are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages--Corndog, Catdawg, Dylan, Firecracker, and YungJamal--designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange.