Infectious bursal disease viruses (IBDVs), belonging to the family Birnaviridae, exhibit a wide range of immunosuppressive potential, pathogenicity, and virulence for chickens. The genomic segment A encodes all the structural (VP2, VP4, and VP3) and nonstructural proteins, whereas segment B encodes the viral RNA-dependent RNA polymerase (VP1). To identify the molecular determinants for the virulence, pathogenic phenotype, and cell tropism of IBDV, we prepared full-length cDNA clones of a virulent strain, Irwin Moulthrop (IM), and constructed several chimeric cDNA clones of segments A and B between the attenuated vaccine strain (D78) and the virulent IM or GLS variant strain. Using the cRNA-based reverse-genetics system developed for IBDV, we generated five chimeric viruses after transfection by electroporation procedures in Vero or chicken embryo fibroblast (CEF) cells, one of which was recovered after propagation in embryonated eggs. To evaluate the characteristics of the recovered viruses in vivo, we inoculated 3-week-old chickens with D78, IM, GLS, or chimeric viruses and analyzed their bursae for pathological lesions 3 days postinfection. Viruses in which VP4, VP4-VP3, and VP1 coding sequences of the virulent strain IM were substituted for the corresponding region in the vaccine strain failed to induce hemorrhagic lesions in the bursa. In contrast, viruses in which the VP2 coding region of the vaccine strain was replaced with the variant GLS or virulent IM strain caused rapid bursal atrophy or hemorrhagic lesions in the bursa, as seen with the variant or classical virulent strain, respectively. These results show that the virulence and pathogenic-phenotype markers of IBDV reside in VP2. Moreover, one of the chimeric viruses containing VP2 sequences of the virulent strain could not be recovered in Vero or CEF cells but was recovered in embryonated eggs, suggesting that VP2 contains the determinants for cell tropism. Similarly, one of the chimeric viruses containing the VP1 segment of the virulent strain could not be recovered in Vero cells but was recovered in CEF cells, suggesting that VP1 contains the determinants for cell-specific replication in Vero cells. By comparing the deduced amino acid sequences of the D78 and IM strains and their reactivities with monoclonal antibody 21, which binds specifically to virulent IBDV, the putative amino acids involved in virulence and cell tropism were identified. Our results indicate that residues Gln at position 253 (Gln253), Asp279, and Ala284 of VP2 are involved in the virulence, cell tropism, and pathogenic phenotype of virulent IBDV.

Infection by the human T-cell leukemia virus type 1 (HTLV-1) is thought to cause dysregulated T-cell proliferation, which in turn leads to adult T-cell leukemia/lymphoma. Early cellular changes after HTLV-1 infection have been difficult to study due to the poorly infectious nature of HTLV-1 and the need for cell-to-cell contact for HTLV-1 transmission. Using a series of reporter systems, we show that HeLa cells cease proliferation within one or two division cycles after infection by HTLV-1 or transduction of the HTLV-1 tax gene. HTLV-1-infected However, T cells containing somatic mutations that inactivate p21CIP1/WAF1 and p27 KIP1 may continue to proliferate after HTLV-1 infection and Tax expression. These infected cells can expand clonally, accumulate additional chromosomal abnormalities, and progress to cancer.Adult T-cell leukemia/lymphoma (ATL) is a rare T-cell malignancy characterized by hypercalcemia, hepatosplenomegaly, lymphadenopathy, skin involvement, and presence of abnormal lymphocytes. ATL develops in 2 to 5% of human T-cell leukemia virus type 1 (HTLV-1)-infected individuals over a clinical latency of 20 to 40 years. The long incubation period and the low frequency of clinical progression to ATL suggest that complex viral and cellular events are involved in ATL development. It has been proposed that after HTLV-1 infection in vivo, at least five independent genetic changes are needed before the onset of ATL (33).The viral determinant critical for the progression to T-cell malignancy in HTLV-1-infected persons is thought to be the HTLV-1 transactivator/oncoprotein, Tax. How Tax influences ATL development is incompletely understood. The effects that Tax exerts over cells are pleiotropic and include potent NF-B activation, cell cycle perturbation, and cell transformation. ATL cells in general do not express HTLV-1 sequence, suggesting that Tax likely affects the early stage of the disease, and persistent Tax expression is not needed for maintenance of the neoplasm (9). Recent data have indicated that an antisense mRNA is transcribed from the 3Ј end of the HTLV-1 provirus.

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The development and progression of alcoholic fatty liver disease (AFLD) is influenced by the intestinal microbiota. Astaxanthin, a type of oxygenated carotenoid with strong antioxidant and anti-inflammatory properties, has been proven to relieve liver injury. However, the relationship between the gut microbiota regulation effect of astaxanthin and AFLD improvement remains unclear. The effects of astaxanthin on the AFLD phenotype, overall structure, and composition of gut microbiota were assessed in ethanol-fed C57BL/6J mice. The results showed that astaxanthin treatment significantly relieves inflammation and decreases excessive lipid accumulation and serum markers of liver injury. Furthermore, astaxanthin was shown to significantly decrease species from the phyla Bacteroidetes and Proteobacteria and the genera Butyricimonas, Bilophila, and Parabacteroides, as well as increase species from Verrucomicrobia and Akkermansia compared with the Et (ethanol)group. Thirteen phylotypes related to inflammation as well as correlated with metabolic parameters were significantly altered by ethanol, and then notably reversed by astaxanthin. Additionally, astaxanthin altered 18 and 128 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways involved in lipid metabolism and xenobiotic biodegradation and metabolism at levels 2 and 3, respectively. These findings suggest that Aakkermansia may be a potential target for the astaxanthin-induced alleviation of AFLD and may be a potential treatment for bacterial disorders induced by AFLD.

A Mg-doped lithium-rich layered oxide material with a stable structure exhibits outstanding electrochemical properties for LIBs.

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