Recombinant IAV H1N1 (A/Brisbane/59/2007) Hemagglutinin (a.a. 18-530) [His]

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and the Korean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measles-mumps-rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

During viral infection, the numbers of virions infecting individual cells can vary significantly over time and space. The functional consequences of this variation in cellular multiplicity of infection (MOI) remain poorly understood. Here, we rigorously quantify the phenotypic consequences of cellular MOI during influenza A virus (IAV) infection over a single round of replication in terms of cell death rates, viral output kinetics, interferon and antiviral effector gene transcription, and superinfection potential. By statistically fitting mathematical models to our data, we precisely define specific functional forms that quantitatively describe the modulation of these phenotypes by MOI at the single cell level. To determine the generality of these functional forms, we compare two distinct cell lines (MDCK cells and A549 cells), both infected with the H1N1 strain A/Puerto Rico/8/1934 (PR8). We find that a model assuming that infected cell death rates are independent of cellular MOI best fits the experimental data in both cell lines. We further observe that a model in which the rate and efficiency of virus production increase with cellular co-infection best fits our observations in MDCK cells, but not in A549 cells. In A549 cells, we also find that induction of type III interferon, but not type I interferon, is highly dependent on cellular MOI, especially at early timepoints. This finding identifies a role for cellular co-infection in shaping the innate immune response to IAV infection. Finally, we show that higher cellular MOI is associated with more potent superinfection exclusion, thus limiting the total number of virions capable of infecting a cell. Overall, this study suggests that the extent of cellular co-infection by influenza viruses may be a critical determinant of both viral production kinetics and cellular infection outcomes in a host cell type-dependent manner. Author summary During influenza A virus (IAV) infection, the number of virions to enter individual cells can be highly variable. Cellular co-infection appears to be common and plays an essential role in facilitating reassortment for IAV, yet little is known about how cellular co-infection influences infection outcomes at the cellular level. Here, we combine quantitativein vitroinfection experiments with statistical model fitting to precisely define the phenotypic consequences of cellular co-infection in two cell lines. We reveal that cellular co-infection can increase and accelerate the efficiency of IAV production in a cell line-dependent fashion, identifying it as a potential determinant of viral replication kinetics. We also show that induction of type III, but not type I, interferon is highly dependent upon the number of virions that infect a given cell, implicating cellular co-infection as an important determinant of the host innate immune response to infection. Altogether, our findings show that cellular co-infection plays a crucial role in determining infection outcome. The integration of experimental and statistical modeling approaches detailed here represents a significant advance in the quantitative study of influenza virus infection and should aid ongoing efforts focused on the construction of mathematical models of IAV infection.