%0 Thesis
%A Moraru, Manuela
%T Susceptibilidad al virus herpes simple tipo 1: contribución de complejos genéticos polimórficos relacionados con la citotoxicidad celular
%D 2016
%U https://hdl.handle.net/20.500.14352/27461
%X El virus Herpes simple tipo 1 (HSV-1) infecta a la mayoría de los individuos en edades tempranas, manteniéndose en estado latente en sus ganglios sensitivos durante toda la vida. La primoinfección requiere un contacto directo entre la piel o las mucosas dañadas de un individuo no infectado con viriones infectivos liberados en los fluidos corporales de un sujeto infectado. Esta infección primaria suele pasar desapercibida o causar sintomatología típica de una infección viral leve. Sin embargo, en casos excepcionales, puede ser la causa de enfermedades graves y potencialmente letales como la encefalitis herpética, el síndrome séptico por HSV-1, la infección congénita, el eczema herpeticum o la queratitis herpética (Abel et al, 2010; Chase et al, 1987; Frederick et al, 2002; Leung et al, 2013, Liesegang et al, 2001; Whitley et al, 1991). El paso del virus a través de las barreras anatómicas de un individuo no infectado es seguido por la replicación viral en el sitio de la inoculación. A continuación, los viriones entran en las fibras nerviosas sensitivas y son transportados hacía los cuerpos neuronales en los ganglios sensitivos, donde se mantienen en estado latente…
%X Herpes Simplex virus type 1 (HSV-1) is a wide-spread human pathogen that infects most adults in early life and establishes life-long latent infection in sensitive ganglia. Quiescent HSV-1 can reactivate periodically in response to certain signals (UV-light exposure, fever, stress) and produce recurrent disease, most often at the site of primary infection. The clinical course of HSV-1 infection varies remarkably, from asymptomatic virion excretion to patients with more than one clinically relevant episode monthly. While the most common clinical picture of HSV-1 reactivation is herpes labialis, a minority of the infected individuals can develop life-threatening episodes of herpetic encephalitis, sepsis-like syndrome, eczema herpeticum, herpetic keratitis or congenital disease. Immunosuppressed individuals are prone to these exacerbated or frequent HSV-1 manifestations, but symptomatic reactivations also occur in many otherwise healthy individuals. Susceptibility to clinically relevant HSV-1 reactivation is thought to depend on the virus itself, environmental factors and host genetics. HSV-1 (Herpesviridae family, Alphaherpesvirinae subfamily) is a large (150-200 nm), spherical, DNA enveloped virus, whose genome includes more than eighty genes. HSV-1 gene transcription follows a stepwise sequence, where three major gene groups are distinguished: immediate early (IE), early and late genes. IE genes are transcribed without prior HSV-1 protein synthesis, as their promoters exploit the host cell transcriptional machinery. IE-gene encoded proteins promote the transcription of early genes and a subset of late genes, which conduct virus DNA and structural proteins synthesis in the productive stage of the infection. Though the classical definition of HSV-1 latency implies viral genome retention in neurons without virion production, there is increasing evidence of limited viral transcription and protein synthesis during this quiescent stage...
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