Cell Culture Replication of a Genotype 1b Hepatitis C Virus Isolate Cloned from a Patient Who Underwent Liver Transplantation

The introduction of the genotype 2a isolate JFH1 was a major breakthrough in the field of hepatitis C virus (HCV), allowing researchers to study the complete life cycle of the virus in cell culture. However, fully competent culture systems encompassing the most therapeutically relevant HCV genotypes are still lacking, especially for the highly drug-resistant genotype 1b. For most isolated HCV clones, efficient replication in cultured hepatoma cells requires the introduction of replication-enhancing mutations. However, such mutations may interfere with viral assembly, as occurs in the case of the genotype 1b isolate Con1. In this study, we show that a clinical serum carrying a genotype 1b virus with an exceptionally high viral load was able to infect Huh7.5 cells. Similar to previous reports, inoculation of Huh7.5 cells by natural virus is very inefficient compared to infection by cell culture HCV. A consensus sequence of a new genotype 1b HCV isolate was cloned from the clinical serum (designated Barcelona HCV1), and then subjected to replication studies. This virus replicated poorly in a transient fashion in Huh7.5 cells after electroporation with in vitro transcribed RNA. Nonetheless, approximately 3 weeks post electroporation and thereafter, core protein-positive cells were detected by immunofluorescence. Surprisingly, small amounts of core protein were also measurable in the supernatant of electroporated cells, suggesting that HCV particles might be assembled and released. Our findings not only enhance the current method of cloning in vitro HCV replication-competent isolates, but also offer valuable insights for the realization of fully competent culture systems for HCV

The diverse meteorology of Jezero crater over the first 250 sols of Perseverance on Mars

ASA’s Perseverance rover’s Mars Environmental Dynamics Analyzer is collecting data at Jezero crater, characterizing the physical processes in the lowest layer of the Martian atmosphere. Here we present measurements from the instrument’s first 250 sols of operation, revealing a spatially and temporally variable meteorology at Jezero. We find that temperature measurements at four heights capture the response of the atmospheric surface layer to multiple phenomena. We observe the transition from a stable night-time thermal inversion to a daytime, highly turbulent convective regime, with large vertical thermal gradients. Measurement of multiple daily optical depths suggests aerosol concentrations are higher in the morning than in the afternoon. Measured wind patterns are driven mainly by local topography, with a small contribution from regional winds. Daily and seasonal variability of relative humidity shows a complex hydrologic cycle. These observations suggest that changes in some local surface properties, such as surface albedo and thermal inertia, play an influential role. On a larger scale, surface pressure measurements show typical signatures of gravity waves and baroclinic eddies in a part of the seasonal cycle previously characterized as low wave activity. These observations, both combined and simultaneous, unveil the diversity of processes driving change on today’s Martian surface at Jezero crater

Real-world evidence of sofosbuvir/velpatasvir as an effective and simple hepatitis C virus treatment and elimination tool in homeless populations

Lay abstract Reducing the prevalence of HCV in people experiencing homelessness is an important step toward elimination of viral hepatitis as a major public health threat. However, several patient and social factors can complicate treatment. Increasing treatment access and cure rates in this population requires treatment regimens to be simple, effective and well tolerated. In this real-world analysis of data collected from 15 clinical cohorts, a once daily 12-week regimen of sofosbuvir/velpatasvir, requiring minimal monitoring, achieved high cure rates across a broad range of HCV-infected people experiencing homelessness.Background: People experiencing homelessness are disproportionately affected by hepatitis C virus (HCV) and can face specific barriers to care. Simple treatment algorithms could increase linkage to care in this population. Methods: This retrospective real-world analysis pooling data from 15 clinical cohorts evaluated effectiveness of a once-daily sofosbuvir/velpatasvir (SOF/VEL) regimen in HCV-infected people experiencing homelessness. The primary outcome was sustained virological response (SVR) in the effectiveness population (patients with confirmed SVR status). Secondary outcomes included reasons for not achieving SVR, adherence and time between diagnosis and SOF/VEL treatment start. Results: Of 153 patients treated with SOF/VEL for 12 weeks without ribavirin, SVR was 100% in the effectiveness population (n = 122), irrespective of various baseline factors including active injecting drug use and presence of mental health disorders. Conclusion: HCV-infected people experiencing homelessness can successfully be treated with SOF/VEL. SOF/VEL enables implementation of simple treatment algorithms and can support test-and-treat strategies through rapid treatment starts and minimal monitoring