ABSTRACT
To investigate community shelter effects of two invasive decapod species, Hemigrapsus sanguineus and Carcinus maenas, in the Long Island Sound (LIS), we deployed artificial shelters in the intertidal and immediate subtidal zones. These consisted of five groups during the summer: a control, a resident H. sanguineus male or female group, and a resident C. maenas male or female group. We quantified utilization of the shelters at 24 h by counting crabs and fish present. We found significant avoidance of H. sanguineus in the field by benthic hermit crabs (Pagurus spp.) and significant avoidance of C. maenas by the seaboard goby (Gobiosoma ginsburgi). The grubby (Myoxocephalus aenaeus) avoided neither treatment, probably since it tends to be a predator of invertebrates. H. sanguineus avoided C. maenas treatments, whereas C. maenas did not avoid any treatment. Seasonal deployments in the subtidal indicated cohabitation of a number of benthic species in the LIS, with peak shelter use corresponding with increased predation and likely reproductive activity in spring and summer for green crabs (C. maenas), hermit crabs (Pagurus spp.), seaboard gobies (G. ginsburgi), and grubbies (Myoxocephalus aenaeus).
ABSTRACT
Telaprevir is a linear, peptidomimetic small molecule that inhibits hepatitis C virus (HCV) replication by specifically inhibiting the NS3·4A protease. In phase 3 clinical studies, telaprevir in combination with peginterferon and ribavirin (PR) significantly improved sustained virologic response (SVR) rates in genotype 1 chronic HCV-infected patients compared with PR alone. In patients who do not achieve SVR after treatment with telaprevir-based regimens, variants with mutations in the NS3·4A protease region have been observed. Such variants can contribute to drug resistance and limit the efficacy of treatment. To gain a better understanding of the viral resistance profile, we conducted phenotypic characterization of the variants using HCV replicons carrying site-directed mutations. The most frequently observed (significantly enriched) telaprevir-resistant variants, V36A/M, T54A/S, R155K/T, and A156S, conferred lower-level resistance (3- to 25-fold), whereas A156T and V36M+R155K conferred higher-level resistance (>25-fold) to telaprevir. Rarely observed (not significantly enriched) variants included V36I/L and I132V, which did not confer resistance to telaprevir; V36C/G, R155G/I/M/S, V36A+T54A, V36L+R155K, T54S+R155K, and R155T+D168N, which conferred lower-level resistance to telaprevir; and A156F/N/V, V36A+R155K/T, V36M+R155T, V36A/M+A156T, T54A+A156S, T54S+A156S/T, and V36M+T54S+R155K, which conferred higher-level resistance to telaprevir. All telaprevir-resistant variants remained fully sensitive to alpha interferon, ribavirin, and HCV NS5B nucleoside and nonnucleoside polymerase inhibitors. In general, the replication capacity of telaprevir-resistant variants was lower than that of the wild-type replicon.
