Tesis doctoral de Ester Aparicio Prats
The role of the hepatitis c virus (hcv) ns3/4a protease in ablating the signaling pathway involved in the production of alpha/beta interferon (ifn-¿/íY) suggests a relationship between ns3/4a proteolytic activity and a patient¿s response to ifn-based therapy. To identify viral factors associated with the hcv treatment response, we analyzed the pretreatment ns3/4a protease gene quasispecies composition of 56 hcv genotype 1¿hiv-1-coinfected patients treated in our clinic with pegylated ifn (pegifn) plus ribavirin (rbv). The catalytic efficiency of the dominant (i.E., The most abundant) quasispecies was also assayed for cardif cleavage and correlated with treatment outcome. A total of 1,745 clones were isolated and sequenced. Significantly less nucleotide quasispecies heterogeneity and lower shannon entropy values were detected within the responder group (p < 0.05). A correlation was also found between the efficiency of ns3/4a protease cardif cleavage and therapy outcome. Proteases from sustained responder patients were more efficient at processing cardif (mean ±standard error of the mean [sem], 0.8960 ±0.05568; n = 19) than proteases from nonresponders (mean ±sem, 0.7269 ±0.05306; n = 37; p < 0.05). Finally, the amino acid p distance (the proportion [p]of nucleotide sites at which two sequences being compared are different) was significantly shorter in patients with an interleukin-28b (il-28b) risk allele (p < 0.01), suggesting that il-28b risk allele carriers exert a lower positive selection pressure on the ns3/4a protease. Ns3/4a protease efficiency in cleaving cardif may be associated with the pegifn-rbv treatment response, as shown in our cohort of hiv-hcvcoinfected patients. Greater ns3/4a nucleotide heterogeneity and higher shannon entropy values in nonresponders suggest that less hcv quasispecies complexity may favor a better response to pegifn-rbv.
Datos académicos de la tesis doctoral «Factors predictius de la resposta al tractament contra el vhc, amb interferó-alfa i ribavirina, amb pacients coinfectats amb vhc i vih-1«
- Título de la tesis: Factors predictius de la resposta al tractament contra el vhc, amb interferó-alfa i ribavirina, amb pacients coinfectats amb vhc i vih-1
- Autor: Ester Aparicio Prats
- Universidad: Autónoma de barcelona
- Fecha de lectura de la tesis: 24/11/2011
Dirección y tribunal
- Director de la tesis
- Miguel ángel Martínez De La Sierra
- Tribunal
- Presidente del tribunal: jordi Gomez castilla
- ramon Planas vila (vocal)
- (vocal)
- (vocal)