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Background: Human Respiratory Syncytial Virus (HRSV) is a major viral pathogen associated with acute lower respiratory tract infections (ALRTI) in children. Using monoclonal antibodies against virus proteins, it is categorized into two distinct major groups, A and B. The second hypervariable region of the G protein ectodomain gene provides a reliable surrogate for phylogenetical studies. We carried out a phylogenetic analysis of the HRSV strains isolated from children hospitalized with ALRTI in Malaysia.Methods: Nasopharyngeal aspirates (NPA) were taken from children less than five years of age hospitalized with ALRTI to Hospital Serdang, Malaysia. RT-PCR was used to detect HRSV. The second hypervariable region at the carboxyl-terminal of the G gene was amplified and sequenced using primer sets GPA/F1 and GPB/F1. Neucleotide sequences were edited and aligned with Bioedite software and Clustal X program. The phylogenetic relationships of the samples were determined separately for group A and B using neighbor joining (NJ), maximum parsimony (MP) and Bayesian methods (BI).Results: HRSV was detected in 83 of 165 (50.3%) patients studied. Sequence analysis of 32 isolates showed that multiple lineages of HRSV group A and B serotypes co-circulated. The topologies resulting from the different methods (NJ, MP and BI) congruent with each other. Phylogenetic analysis of nine retrieved sequences showed that all the HRSV-A strains were clustered into the NA1 genotype. All the 23 HRSV-B strains belonged to BA genotypes consisted of a 60-nucleotide duplication region. They were classified into three different genotypes of BA10, BA9 and BA4, respectively.Conclusion: HRSV played a prominent role for hospitalization of children in our study. The sequences of the second hypervariable region of G protein ectodomain gene from HRSV A and B demonstrated remarkable genetic diversity. The present finding seems to be consistent with other studies which found the newly emerged HRSV genotypes of NA1 and BA genotypes are replacing the previously dominant genotypes. This is the first documentation of the phylogenetic relationship and genetic diversity of HRSV isolates among hospitalized children diagnosed with ALRTI in Malaysia.

SummaryThe IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon’s protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections.

Stem cell differentiation and lineage specification depend on coordinated programs of gene expression, but our knowledge of the chromatin-modifying factors regulating these events remains incomplete. Ubiquitination of histone H2A (H2A-K119u) is a common chromatin modification associated with gene silencing, and controlled by the ubiquitin-ligase polycomb repressor complex 1 (PRC1) and H2A-deubiquitinating enzymes (H2A-DUBs). The roles of H2A-DUBs in mammalian development, stem cells, and hematopoiesis have not been addressed. Here we characterized an H2A-DUB targeted mouse line Mysm1(tm1a/tm1a) and demonstrated defects in BM hematopoiesis, resulting in lymphopenia, anemia, and thrombocytosis. Development of lymphocytes was impaired from the earliest stages of their differentiation, and there was also a depletion of erythroid cells and a defect in erythroid progenitor function. These phenotypes resulted from a cell-intrinsic requirement for Mysm1 in the BM. Importantly, Mysm1(tm1a/tm1a) HSCs were functionally impaired, and this was associated with elevated levels of reactive oxygen species, γH2AX DNA damage marker, and p53 protein in the hematopoietic progenitors. Overall, these data establish a role for Mysm1 in the maintenance of BM stem cell function, in the control of oxidative stress and genetic stability in hematopoietic progenitors, and in the development of lymphoid and erythroid lineages.