Viruses are leading causes of severe acute lower respiratory infections (LRIs). These infections evoke incomplete immunity, as individuals can be repeatedly reinfected throughout life. We report that acute viral LRI causes rapid pulmonary CD8 + cytotoxic T lymphocyte (T CD8 ) functional impairment via programmed death-1/ programmed death ligand-1 (PD-1/PD-L1) signaling, a pathway previously associated with prolonged antigenic stimulation during chronic infections and cancer. PD-1-mediated T CD8 impairment occurred acutely in mice following infection with human metapneumovirus or influenza virus. Viral antigen was sufficient for PD-1 upregulation, but induction of PD-L1 was required for impairment. During secondary viral infection or epitope-only challenge, memory T CD8 rapidly reexpressed PD-1 and exhibited severe functional impairment. Inhibition of PD-1 signaling using monoclonal antibody blockade prevented T CD8 impairment, reduced viral titers during primary infection, and enhanced protection of immunized mice against challenge infection. Additionally, PD-1 and PD-L1 were upregulated in the lungs of patients with 2009 H1N1 influenza virus, respiratory syncytial virus, or parainfluenza virus infection. These results indicate that PD-1 mediates T CD8 functional impairment during acute viral infection and may contribute to recurrent viral LRIs. Therefore, the PD-1/PD-L1 pathway may represent a therapeutic target in the treatment of respiratory viruses.

Five kittens exposed neonatally to older cats exhibiting fever with nasal and ocular discharge became ill and died within 10 days of the onset of illness. One kitten which died at 16 days old was examined post mortem and feline herpesvirus 1 was isolated from the brain, liver, lung and spleen.

Melissa Downing is a Senior Project Archivist at the University of Melbourne's eScholarship Research Centre. Melissa's current project role is Database Manager for the 'Find & Connect' web resource. She recently provided archival training for non-government organisations as part of the Records Access Documentation Project to improve access to records of Forgotten Australians and former child migrants. In 2012, she worked with ten community service organisations in Victoria to complete the Self-Assessment Tool for Archives. Michael Jones is a Senior Research Archivist at the University of Melbourne's eScholarship Research Centre and Acting Program Manager of the 'Find & Connect' web resource from 2012 to 2013. Since starting at the Centre in 2008, he has worked on numerous paper-based and digital archival projects with academics, government departments and arts and community organisations to explore the potential of structured informatic systems to support organisational and public knowledge.Cathy Humphreys is the Alfred Felton Chair of Child and Family Welfarea professorship established through collaboration between the Department of Social Work at the University of Melbourne and the Centre for Excellence for Child and Family Welfare in Victoriathe peak body for 90 child and family welfare agencies. She has developed a strand of research in the area of out-of-home care, where her interest in documentary analysis continues to be explored. The Who Am I? project was led by Cathy Humphreys and evolved to bring the highly significant, but neglected, area of recordkeeping in out-of-home care to the fore.

Viruses are leading causes of severe acute lower respiratory infection (LRI) yet evoke incomplete immunity as individuals can be repeatedly reinfected throughout life. We report that acute viral LRI causes rapid CD8+ cytotoxic T lymphocyte (CTL) functional impairment in the respiratory tract via programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling, a pathway previously associated with prolonged antigenic stimulation during chronic infections and cancer. PD-1-mediated pulmonary CTL impairment occurred as early as day 7 during human metapneumovirus or influenza virus infections. Viral antigen alone was sufficient to drive PD-1 upregulation, but PD-1 ligation by infection-induced PD-L1 was required for impairment. Therapeutic inhibition of PD-1 signaling prevented CTL impairment and reduced viral titers without exacerbating lower airway pathology. Additionally, PD-1 and PD-L1 were upregulated in the lungs of pediatric patients with severe H1N1 pandemic influenza virus or respiratory syncytial virus infections. Our results indicate that PD-1 signaling mediates CTL functional impairment rapidly at primary sites of infection due to the presence of local viral antigen and represents a conserved response against different viruses that cause serious LRI in children and adults. Therefore, the PD-1/PD-L1 pathway may represent a novel target for therapeutics and vaccine development against respiratory viruses.