RESUMEN
Infection of cells by herpes simplex virus type 1 (HSV-1) triggers host cell shutoff whereby mRNAs are degraded and cellular protein synthesis is diminished. However, virus protein translation continues because the translational apparatus in HSV-infected cells is maintained in an active state. Surprisingly, poly(A)-binding protein 1 (PABP1), a predominantly cytoplasmic protein that is required for efficient translation initiation, is partially relocated to the nucleus during HSV-1 infection. This relocalization occurred in a time-dependent manner with respect to virus infection. Since HSV-1 infection causes cell stress, we examined other cell stress inducers and found that oxidative stress similarly relocated PABP1. An examination of stress-induced kinases revealed similarities in HSV-1 infection and oxidative stress activation of JNK and p38 mitogen-activated protein (MAP) kinases. Importantly, PABP relocalization in infection was found to be independent of the viral protein ICP27. The depletion of PABP1 by small interfering RNA (siRNA) knockdown had no significant effect on viral replication or the expression of selected virus late proteins, suggesting that reduced levels of cytoplasmic PABP1 are tolerated during infection.
Asunto(s)
Núcleo Celular/metabolismo , Herpes Simple/metabolismo , Herpesvirus Humano 1/fisiología , Proteínas Inmediatas-Precoces/metabolismo , Proteína I de Unión a Poli(A)/metabolismo , Replicación Viral , Animales , Proteínas Portadoras , Núcleo Celular/genética , Chlorocebus aethiops , Regulación Viral de la Expresión Génica , Células HeLa , Herpes Simple/virología , Herpesvirus Humano 1/genética , Humanos , Proteínas Inmediatas-Precoces/genética , Estrés Oxidativo , Proteína I de Unión a Poli(A)/genética , Transporte de Proteínas , Células VeroRESUMEN
The evolution serological response against the herpes simplex virus and citomegalovirus in HIV infected patients grouped into different stages of the disease was studied. Fluctuations in the TPG of antibodies were observed in these values in a cyclical way through time. There was a greater significant difference among the TPG of antibodies against HSV in the group of asymptomatic patients compared with AIDS patients and with those who died. There is a marked decrease in the TPG of antibodies against HSV and CMV approximately one year before the death of patients.