RESUMEN
Human immunodeficiency virus effectively evades CD8(+) T-cell responses through the development of CD8 escape mutations. Recent reports documenting reversion of transmitted mutations and the impact of specific escape mutations upon viral replication suggest that complex forces limit the accumulation of CD8 escape mutations at the population level. However, the presence of compensatory mutations capable of alleviating the impact of CD8 escape mutations on replication capacity may enable their persistence in an HLA-mismatched host. Herein, we illustrate the long-term stability of stereotypic escape mutations in the immunodominant HLA-B27-restricted epitope KK10 in p24/Gag following transmission when accompanied by a specific compensatory mutation.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/genética , Epítopos de Linfocito T/inmunología , VIH/crecimiento & desarrollo , VIH/inmunología , Mutación Missense/inmunología , Secuencia de Aminoácidos , Animales , VIH/genética , Proteína p24 del Núcleo del VIH/genética , Humanos , Datos de Secuencia Molecular , Replicación ViralAsunto(s)
Aneurisma de la Aorta Torácica/terapia , Fístula Esofágica/terapia , Cuidados Paliativos/métodos , Stents , Fístula Vascular/terapia , Anciano , Anastomosis Quirúrgica , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Implantación de Prótesis Vascular/métodos , Servicio de Urgencia en Hospital , Fístula Esofágica/diagnóstico , Esofagectomía/métodos , Esofagoscopía/métodos , Estudios de Seguimiento , Hematemesis/diagnóstico , Hematemesis/etiología , Humanos , Masculino , Retratamiento , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Fístula Vascular/diagnósticoRESUMEN
BACKGROUND: CD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the different HIV-1 clades distributed world-wide. Unfortunately, little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: To identify dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected subjects we drew upon data from an immunological screen of 100 HIV-1 clade CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24, (277)YSPVSILDI(285), YI9). Over 75% of Cw*0102+ve subjects targeted this epitope, representing the strongest response in more than a third of these individuals. This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57 and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was frequently observed in Cw*0102+ve subjects, suggestive of strong selection pressure being exerted by this common CD8+ T cell response. CONCLUSIONS/SIGNIFICANCE: As HLA-Cw*0102 is frequently expressed in the Thai population (allelic frequency of 16.8%), this immunodominant Cw*0102-restricted Gag epitope may represent an attractive candidate for vaccines specific to CRF01_AE and may help facilitate further studies of immunopathogenesis in this understudied HIV-1 clade.