The role of M2-2 PDZ-binding motifs in pulmonary innate immune responses to human metapneumovirus.

Human metapneumovirus (HMPV) is a leading cause of lower respiratory tract infection (LRTI) in pediatric and geriatric populations. We recently found that two PDZ-binding motifs of the M2-2 protein, 29-DEMI-32 and 39-KEALSDGI-46, play a significant role in mediating HMPV immune evasion in airway epithelial cells (AECs). However, their role in the overall pulmonary responses to HMPV infection has not been investigated. In this study, we found that two recombinant HMPVs (rHMPV) lacking the individual M2-2 PDZ-binding motif are attenuated in mouse lungs. Mice infected with mutants produce more cytokines/chemokines in bronchoalveolar lavage (BAL) fluid compared to mice infected with wild-type rHMPV. In addition, both mutants are able to enhance the pulmonary recruitment of dendritic cells (DCs) and T cells and induce effective protections against the HMPV challenge. The DC maturation is also significantly improved by the motif mutation. Taken together, our data provide proof-of-principle for two live-attenuated M2-2 mutants to be promising HMPV vaccine candidates that are effective in inducing higher pulmonary innate immunity and generating protection against HMPV infection.

The effects in correction of anaemia in chronic kidney disease with erythropoietin therapy--preference to cardiovascular, neurologic and general well-being of patients from a tertiary care centre.

Anaemia, the major sequelae of chronic renal disease (CRD) needs to be investigated because it acts as an independent risk factor for worsening of cardiovascular survival, cognitive impairment and poor quality of life. In this prospective tertiary care hospital-based study we have followed up 100 randomly assigned CRD patients who were not on dialysis for at least 6 months. Left ventricular mass index (LVMI), ejection fraction (EF), mini-mental status examination (MMSE) and general well-being of these patients were assessed quantitatively on admission and at 3rd and 6th months of follow-up after receiving recombinant human erythropoietin (rHuEPO) and aggressive intravenous iron therapy for anaemia correction. The median study duration was 6 years. Statistical analysis also showed the positive impact of anaemia correction which, even when partial, caused significant improvement in cardiovascular function as evidenced by increase in EF (p = 0.004) and decrease in LVMI (p = 0.016) along with substantial enhancement of general well-being (p < 0.001). Cognition did not show significant change within a short spell of 6 months. This study thus emphasises on earliest detection and correction of anaemia in CRD population to enhance both short-term and long-term survival as a whole.