Retreatment of patients with chronic hepatitis C, subtype 3a, and cirrhosis, who previously failed a regimen containing second-generation NS5A inhibitors with sofosbuvir + glecaprevir/pibrentasvir and ribavirin for 16-24 weeks.

The outcomes of retreatment patients infected with hepatitis C virus genotype 3, cirrhosis, with velpatasvir may be affected by treatment failure with velpatasvir. The efficacy of SOF+GLE/PIB+RIB 16-24 weeks of treatment has been shown. The presence of NS5A resistance-associated substitution mutations, including Y93H, and the number and regimens of the past failed therapy do not influence the likelihood of achieving sustained virological response.

CD8 T Cells Mediate Lethal Lung Pathology in the Absence of PD-L1 and Type I Interferon Signalling following LCMV Infection.

CD8 T cells are critical to the adaptive immune response against viral pathogens. However, overwhelming antigen exposure can result in their exhaustion, characterised by reduced effector function, failure to clear virus, and the upregulation of inhibitory receptors, including programmed cell death 1 (PD-1). However, exhausted T cell responses can be "re-invigorated" by inhibiting PD-1 or the primary ligand of PD-1: PD-L1.

Complexities of Type I Interferon Biology: Lessons from LCMV.

Over the past decades, infection of mice with lymphocytic choriomeningitis virus (LCMV) has provided an invaluable insight into our understanding of immune responses to viruses. In particular, this model has clarified the central roles that type I interferons play in initiating and regulating host responses. The use of different strains of LCMV and routes of infection has allowed us to understand how type I interferons are critical in controlling virus replication and fostering effective antiviral immunity, but also how they promote virus persistence and functional exhaustion of the immune response.

Collateral Damage: What Effect Does Anti-CD4 and Anti-CD8α Antibody-Mediated Depletion Have on Leukocyte Populations?

Anti-CD4 or anti-CD8α Ab-mediated depletion strategies are widely used to determine the role of T cell subsets. However, surface expression of CD4 and CD8α is not limited to T cells and occurs on other leukocyte populations as well. Using both unbiased -distributed stochastic neighbor embedding of flow cytometry data and conventional gating strategies, we assessed the impact of anti-CD4 and anti-CD8α Ab-mediated depletion on non-T cell populations in mice.

IRF9 Prevents CD8 T Cell Exhaustion in an Extrinsic Manner during Acute Lymphocytic Choriomeningitis Virus Infection.

Effective CD8 T cell responses play an important role in determining the course of a viral infection. Overwhelming antigen exposure can result in suboptimal CD8 T cell responses, leading to chronic infection. This altered CD8 T cell differentiation state, termed exhaustion, is characterized by reduced effector function, upregulation of inhibitory receptors, and altered expression of transcription factors.