Up-regulation of interleukin-8 by novel small cytoplasmic molecules of nontypeable Haemophilus influenzae via p38 and extracellular signal-regulated kinase pathways.
In vitro, the antiviral effect of p38 MAPK inhibitor BCT194 was evaluated in differentiated human bronchial epithelial cells (HBECs); in vivo, female BALB/c mice were infected intranasally with 150 pfu of influenza H1N1 A/Puerto Rico/8/34 and treated with BCT197 (a closely related p38 MAPK inhibitor with an IC50 value of<1 µM, currently in clinical testing), dexamethasone or oseltamivir (Tamiflu) starting 24 h post infection.
The manipulation of this pathway may be useful for regulating AID abundance and efficiency of Ig class switching and is therefore a potential target for developing immunologic adjuvants for vaccines of various pathogens such as HIV-1 and influenza viruses.
Collectively, our results demonstrate that influenza infection activates the AIM2 inflammasome, which plays a critical role in IAV-induced lung injury and mortality.
In vitro, the antiviral effect of p38 MAPK inhibitor BCT194 was evaluated in differentiated human bronchial epithelial cells (HBECs); in vivo, female BALB/c mice were infected intranasally with 150 pfu of influenza H1N1 A/Puerto Rico/8/34 and treated with BCT197 (a closely related p38 MAPK inhibitor with an IC50 value of<1 µM, currently in clinical testing), dexamethasone or oseltamivir (Tamiflu) starting 24 h post infection.
Up-regulation of interleukin-8 by novel small cytoplasmic molecules of nontypeable Haemophilus influenzae via p38 and extracellular signal-regulated kinase pathways.
We therefore explore the functional sequence space of bnAb C05, which targets the receptor-binding site (RBS) of influenza haemagglutinin (HA) via a long CDR H3.
The mutation also resulted in a reduced ability to utilize haem, haem-haemopexin, haem-albumin and haemoglobin-haptoglobin, thus identifying a general haem-utilization protein (Hup) in Haemophilus influenzae.
The inclusion of 0.1% SDS resulted in maximal influenza RNA recovery (41.3%) but with a complete loss of infectivity whereas inclusion of 0.1% bovine serum albumin resulted in reduced RNA recovery (6.8%) but maximal retention of virus infectivity (17.9%).
When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 <sup>-/-</sup> mice than in WT mice.
When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i) bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii) hemagglutinin (HA) of influenza virus and (iii) the extracellular domain of anaplastic lymphoma kinase (ALK).
Using a CRISPR approach, we show that the human <u>a</u>cidic <u>n</u>uclear <u>p</u>hosphoproteins (ANPs) ANP32A and ANP32B are functionally redundant but essential host factors for mammalian-adapted influenza A virus (IAV) and influenza B virus (IBV) replication in human cells.
Using a CRISPR approach, we show that the human <u>a</u>cidic <u>n</u>uclear <u>p</u>hosphoproteins (ANPs) ANP32A and ANP32B are functionally redundant but essential host factors for mammalian-adapted influenza A virus (IAV) and influenza B virus (IBV) replication in human cells.
Human ANP32A and ANP32B homologues both support function of human-adapted influenza polymerase but do not support efficient activity of avian IAV polymerase which requires avian ANP32A.