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The effects of dexamethasone (DXM) treatment on pulmonary immunity in COVID-19–associated acute respiratory distress syndrome (CARDS) remain insufficiently understood. We performed transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid from 20 mechanically ventilated patients: 12 with CARDS (with or without DXM) and 8 non–COVID-19 critically ill controls. CARDS with DXM was characterized by upregulation of genes related to B-cell and complement pathway activation, antigen presentation, phagocytosis, and FC-γ receptor signaling. Most interferon-stimulated genes were upregulated in CARDS, particularly in CARDS without DXM. In conclusion, DXM treatment was not associated with regulation of proinflammatory pathways in CARDS but with regulation of other local immune responses. Clinical Trials Registration. NCT04354584. [ABSTRACT FROM AUTHOR]

Global control of hepatitis C virus (HCV) depends on development of a prophylactic vaccine. We studied escape for cross-genotype-reactive neutralizing antibody AR4A, providing valuable information for HCV vaccine design. We cultured HCV core-NS2 recombinants H77 (genotype 1a)/JFH1 or the highly antibody-susceptible hypervariable region 1 (HVR1)-deleted variants H77/JFH1∆HVR1 and J6(genotype 2a)/JFH1∆HVR1 in Huh7.5 cells with AR4A. Long-term AR4A exposure of H77/JFH1 and H77/JFH1∆HVR1 did not yield resistance. However, J6/JFH1∆HVR1 developed the envelope-E2 substitutions I696T or I696N, which reduced AR4A binding (I696N > I696T). I696N conferred greater AR4A resistance than I696T in J6/JFH1∆HVR1, whereas the reverse was observed in J6/JFH1. This was because I696N but not I696T conferred broadly increased antibody neutralization susceptibility to J6/JFH1. I696N and I696T abrogated infectivity of H77/JFH1 and broadly increased neutralization susceptibility of S52 (genotype 3a)/JFH1. In conclusion, I696 is in the AR4A epitope, which has a high barrier to resistance, thus strengthening the rationale for its inclusion in rational HCV vaccine designs. [ABSTRACT FROM AUTHOR]

Little is known about the presence and role of neutralizing antibodies (NtAbs) in perinatal hepatitis C virus (HCV) infection. Using HCV pseudoparticles, NtAbs were studied longitudinally in 12 HCV-infected children with or without evidence of acute hepatitis during the first year of life. Broadly reactive NtAbs of maternal origin did not prevent vertical HCV transmission or progression to chronicity. NtAbs against homologous genotype or subtype appeared during the chronic phase and were more abundant and sustained in children with acute hepatitis. Cross-reactive NtAbs were present in both groups of children, but their appearance did not correlate with better control of viremia or HCV clearance. [ABSTRACT FROM AUTHOR]

We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2 envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1 challenge, were initially studied using the heterologous H77 (genotype 1a) HCVpp assay. All animals had developed NtAb after the second vaccination; 4 animals had reciprocal titers of ≥200 at the time of challenge. Using genotypes 1a-6a HCV pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) assays, cross-reactive NtAb were detected against 1a, 4a, 5a, and 6a, with limited reactivity against 2a and 3a. Our study provides encouragement for the development of a recombinant envelope-based vaccine against hepatitis C. [ABSTRACT FROM AUTHOR]

Investigates the genetic epidemiology of hepatitis C virus (HCV) throughout Egypt. Characterization of HCV genotype distribution and concordance of genotype assessments on the basis of multiple genomic regions; Amplification of the 5' noncoding, core/E1 and NS5B regions; Results of the phylogenetic analyses of the core/E1 and NS5B regions; Consistency of the genetic distance between isolates.

Six major genotypes (genotypes 1–6) of hepatitis C virus (HCV) have been identified. These genetic variants are being transmitted to chimpanzees, the only recognized animal model for the study of HCV. Genotype 5a (strain SA13), a variant found primarily in South Africa, has been transmitted to chimpanzees for the first time. Experimental infection of 2 chimpanzees was characterized by early appearance of viremia and peak virus titers of 105–106 genome equivalents/mL. The HCV infection was resolved by week 15 after inoculation in 1 chimpanzee and persisted in the other. Both chimpanzees became anti-HCV—positive by week 14 after inoculation. Both chimpanzees developed viral hepatitis. The infectivity titer of a genotype 5a challenge pool prepared from the first passage of HCV in a chimpanzee was ∼104 infectious doses/mL. Finally, sequence analysis of strain SA13 confirmed that genotype 5a is genetically distinct from other genotypes of HCV. [ABSTRACT FROM PUBLISHER]

Hepatitis G virus (HGV) was transmitted to 2 chimpanzees by inoculation with human plasma containing ∼108 genome equivalents (GE) of HGV. The infection was characterized by the late appearance (weeks 10 and 11 after inoculation [pi]) of viremia that persisted throughout the 120-week follow-up. Serum HGV titer increased steadily until it plateaued at 106–107 GE/mL. However, despite this relatively high titer, neither of the chimpanzees developed hepatitis. The sequence of the viral genome, recovered from each chimpanzee at week 77 pi, differed from that of the inoculum by 5 nt (2 aa) and 27 nt (2 aa). Two more chimpanzees were inoculated with a first-passage plasma pool. The chimpanzee inoculated with ∼106.7 GE of HGV had viremia at week 1 pi. However, the viral titer increased with the same kinetics as observed in the first passage. The second chimpanzee inoculated with ∼104.7 GE of HGV had late appearance (week 7 pi) of viremia. [ABSTRACT FROM PUBLISHER]

The establishment of cell cultures for hepatitis C virus (HCV) is important for its study as a human pathogen. However, in reported cell lines, HCV demonstrates low levels of replication detected primarily by reverse transcription-polymerase chain reaction (RT-PCR) assays. In attempts to culture HeV, an additional complication was observed. From mock-infected cultures, cDNA of appropriate size was obtained by RT-PCR with primers deduced from conserved domains of the 5' noncoding region of HCV. However, sequence analysis revealed that the cDNA was amplified from bovine viral diarrhea virus (BVDV). All of 7 bovine sera tested were contaminated with BVDV. In conclusion, most commercially available bovine sera are contaminated with BVDV and, although there is no evidence that the virus is infectious, bovine sera should be screened for this virus by RT-PCR when used in conjunction with HCV or for the development or production of vaccine. [ABSTRACT FROM PUBLISHER]

Results of serologic tests were correlated with hepatitis C virus (HCV) viremia, determined by a cDNA polymerase chain reaction assay to detect HCV RNA, in 340 Danish dialysis patients; of these, 28 (8.2%) were positive for antibodies to HCV (anti-HCV) with second-generation ELISAse HCV RNA was found in sera from 27 of these 28 anti-HCV-positive patients. However, 8 dialysis patients had detectable levels of HCV RNA but were anti-HCV-negative with secondgeneration ELISAs. Among the 35 HCV-infected dialysis patients 16 were positive, 7 indeterminate, and 12 negative with the second-generation RIBA. More than 60% of patients with evidence of ongoing liver disease had HCV infection. Thus, current commercially available antibody tests did not accurately reflect the HCV status in dialysis patients. A relatively high prevalence (> 10%)ofHCV RNA, closely associated with liver disease, was found among dialysis patients in a low-prevalence area of the world. [ABSTRACT FROM PUBLISHER]

The effects of dexamethasone (DXM) treatment on pulmonary immunity in COVID-19-associated acute respiratory distress syndrome (CARDS) remain insufficiently understood. We performed transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid from 20 mechanically ventilated patients: 12 with CARDS (with or without DXM) and 8 non-COVID-19 critically ill controls. CARDS with DXM was characterized by upregulation of genes related to B-cell and complement pathway activation, antigen presentation, phagocytosis, and FC-γ receptor signaling. Most interferon-stimulated genes were upregulated in CARDS, particularly in CARDS without DXM. In conclusion, DXM treatment was not associated with regulation of proinflammatory pathways in CARDS but with regulation of other local immune responses. Clinical Trials Registration. NCT04354584., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)