Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response

Membrane rafts are small (10–200 nm) sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts play an important role in viral infection cycles and viral virulence. Viruses are divided into four main classes, enveloped DNA virus, enveloped RNA virus, nonenveloped DNA virus, and nonenveloped RNA virus. General virus infection cycle is also classified into two sections, the early stage (entry process) and the late stage (assembly, budding, and release processes of virus particles). In the viral cycle, membrane rafts act as a scaffold of many cellular signal transductions, which are associated with symptoms caused by viral infections. In this paper, we describe the functions of membrane rafts in viral lifecycles and host cellular response according to each virus classification, each stage of the virus lifecycle, and each virus-induced signal transduction

Mechanisms of the action of povidone-iodine against human and avian influenza A viruses: its effects on hemagglutination and sialidase activities

<p>Abstract</p> <p>Background</p> <p>Influenza virus infection causes significant morbidity and mortality and has marked social and economic impacts throughout the world. The influenza surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), act cooperatively to support efficient influenza A virus replication and provide the most important targets for anti-influenza chemotherapy. In this study, povidone-iodine (PVP-I), which has a broad-spectrum microbicidal property, was examined for its inhibitory effects against influenza virus infection in MDCK cells and the mechanisms of PVP-I action on HA and NA were revealed.</p> <p>Results</p> <p>Results obtained using a novel fluorescence- and chromogenic-based plaque inhibition assay showed that 1.56 mg/ml PVP-I inhibited infections in MDCK cells of human (8 strains) and avian (5 strains) influenza A viruses, including H1N1, H3N2, H5N3 and H9N2, from 23.0–97.5%. A sialidase inhibition assay revealed that PVP-I inhibited N1, N2 and N3 neuraminidases with IC₅₀values of 9.5–212.1 μg/ml by a mixed-type inhibition mechanism. Receptor binding inhibition and hemagglutinin inhibition assays indicated that PVP-I affected viral hemagglutinin rather than host-specific sialic acid receptors.</p> <p>Conclusion</p> <p>Mechanisms of reduction of viral growth in MDCK cells by PVP-I involve blockade of viral attachment to cellular receptors and inhibition of viral release and spread from infected cells. Therefore, PVP-I is useful to prevent infection and limit spread of human and avian influenza viruses.</p

The Low-pH Stability Discovered in Neuraminidase of 1918 Pandemic Influenza A Virus Enhances Virus Replication

The “Spanish” pandemic influenza A virus, which killed more than 20 million worldwide in 1918-19, is one of the serious pathogens in recorded history. Characterization of the 1918 pandemic virus reconstructed by reverse genetics showed that PB1, hemagglutinin (HA), and neuraminidase (NA) genes contributed to the viral replication and virulence of the 1918 pandemic influenza virus. However, the function of the NA gene has remained unknown. Here we show that the avian-like low-pH stability of sialidase activity discovered in the 1918 pandemic virus NA contributes to the viral replication efficiency. We found that deletion of Thr at position 435 or deletion of Gly at position 455 in the 1918 pandemic virus NA was related to the low-pH stability of the sialidase activity in the 1918 pandemic virus NA by comparison with the sequences of other human N1 NAs and sialidase activity of chimeric constructs. Both amino acids were located in or near the amino acid resides that were important for stabilization of the native tetramer structure in a low-pH condition like the N2 NAs of pandemic viruses that emerged in 1957 and 1968. Two reverse-genetic viruses were generated from a genetic background of A/WSN/33 (H1N1) that included low-pH-unstable N1 NA from A/USSR/92/77 (H1N1) and its counterpart N1 NA in which sialidase activity was converted to a low-pH-stable property by a deletion and substitutions of two amino acid residues at position 435 and 455 related to the low-pH stability of the sialidase activity in 1918 NA. The mutant virus that included “Spanish Flu”-like low-pH-stable NA showed remarkable replication in comparison with the mutant virus that included low-pH-unstable N1 NA. Our results suggest that the avian-like low-pH stability of sialidase activity in the 1918 pandemic virus NA contributes to the viral replication efficiency

コキュウ コンナン オ ケイキ ニ ハッケンサレ シュウガクテキ チリョウ ニヨリ カンカイ シタ シンコウ セイソウ ガン ノ 1レイ

A 30-year-old man was referred to our hospital for examination and treatment of dyspnea.Clinical examination revealed multiple lung tumor masses with marked elevation -HCG and -fetoprotein. CT showed not only multiple lung tumors but also retroperitoneal tumor mass. Apercutaneous needle biopsy of lung tumor was performed and pathological findings suggestedchoriocarcinoma. Although testicular swelling was not detected, ultrasonography revealed a righttesticular mass lesion. Therefore we diagnosed multiple lung metastases from right testicularcancer with retroperitoneal lymph node metastasis. The induction chemotherapy with bleomycin,etoposide, cisplatin（BEP） for 3 cycles was performed. Subsequently second line chemotherapywith paclitaxel, ifosfamide, nedaplatin（TIN）for 8 cycles followed. After the tumor markers werenormalized, resection of residual lung metastases by video-assisted thoracic surgery（VATS）andright high orchiectomy were performed. Histologically no viable cells were detected. One cyclechemotherapy with TIN was given after first surgery. Secondly, retroperitoneal lymph nodedissection was performed, and pathologically the small amount of viable cancer was detected in theresected specimen. Then post operative chemotherapy with TIN for 2 cycles were performed.The patient is alive without any recurrence 3 years after combined modality therapy