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R Shimano

Publications and source records attributed to R Shimano.

29 records · Page 2Linked to original sources

The non-env tropism of HIV/SIV (Review).

The tropism of human and simian immunodeficiency viruses (HIV and SIV) determined by sequences other than env has been studied. The restriction of HIV-1 replication in monkey cells was demonstrated to be regulated by viral non-env sequence. Likewise, the gag-pol region of SIVagm (virus of the African green monkey) genome was found to be responsible for growth restriction in human cells of the virus. No viral DNA synthesis was detected in cells nonpermissive for the viruses. In addition, a number of HIV-1 gag gene mutants, which have an early defect in viral replication cycle and direct no viral DNA synthesis in some cells, exhibited a phenotype of host range mutant. Taken together, it can be concluded that the viral tropism associated with the uncoating/ reverse transcription process does exist in HIV/SIV replication. Furthermore, many of the accessory gene mutants of HIV/SIV exhibit host cell-dependent replication property. In this review, we summarize these examples of non-env tropism of HIV/SIV.

Animals↗

Functional domain mapping of HIV-1 Gag proteins.

A series of human immunodeficiency virus type 1 (HIV-1) proviral gag gene mutants carrying bacterial CAT gene were constructed and monitored for the expression of reverse transcriptase and CAT in a highly sensitive single-round replication assay system to determine the defective replication phase in lymphocytic cells. All the mutants displayed no abnormality in the process of transcription and translation at late replication stage. In contrast, some matrix, capsid, and p6 mutants were defective at final phase, that is, assembly and virion release. Most of the mutants including nucleocapsid mutants, which showed normal phenotype at late stage, were defective at early replication phase. From the functional domain map thus obtained, it is evident that HIV-1 Gag proteins are required for both early and late replication phases.

CD4-Positive T-Lymphocytes↗

Cleavage of Gag precursor is required for early replication phase of HIV-1.

A mutant of human immunodeficiency virus type 1 (HIV-1), which is deficient for Gag precursor cleavage and noninfectious, was characterized with respect to its defective step in the viral replication phase. Upon transfection, the mutant produced a normal level of progeny virions as monitored by electron microscopy and RNA hybridization. Single-round replication assay demonstrated, in contrast, that the mutant was defective at the early phase of the replication cycle. Furthermore, no viral DNA was detected in the cells infected with the mutant. Taken together, it is concluded that maturation of Gag precursor protein of HIV-1 is required for an early event(s) before or during a coupled process of uncoating/reverse transcription.

Blotting, Southern↗

HIV-1 capsid mutants inhibit the replication of wild-type virus at both early and late infection phases.

In-frame mutations were introduced into various portions of the human immunodeficiency virus type 1 (HIV-1) gag gene, and potentials of the mutants to suppress the replication of wild-type HIV-1 were monitored. In contrast to results obtained with matrix and nucleocapsid mutants, almost all capsid mutants blocked HIV-1 replication completely in single-round replication assays. A capsid mutant designated C6b was demonstrated to be one of the most efficient inhibitors for HIV-1 reported to date, and to be effective at both early and late viral replication phases. T-cells, which are engineered to express the C6b Gag in response to HIV-1 infection, were perfectly resistant to HIV-1.

Blotting, Western↗

Antibacterial activity of xanthones from guttiferaeous plants against methicillin-resistant Staphylococcus aureus.

Extracts of Garcinia mangostana (Guttiferae) showing inhibitory effects against the growth of S. aureus NIHJ 209p were fractionated according to guidance obtained from bioassay and some of the components with activity against methicillin-resistant Staphylococcus aureus (MRSA) were characterized. One active isolate, alpha-mangostin, a xanthone derivative, had a minimum inhibitory concentration (MIC) of 1.57-12.5 micrograms mL-1. Other related xanthones were also examined to determine their anti-MRSA activity. Rubraxanthone, which was isolated from Garcinia dioica and has a structure similar to that of alpha-mangostin, had the highest activity against staphylococcal strains (MIC = 0.31-1.25 micrograms mL-1), an activity which was greater than that of the antibiotic vancomycin (3.13-6.25 micrograms mL-1). The inhibitory effect against strains of MRSA of two of the compounds when used in conjunction with other antibiotics was also studied. The anti-MRSA activity of alpha-mangostin was clearly increased by the presence of vancomycin; this behaviour was not observed for rubraxanthone. The strong in-vitro antibacterial activity of xanthone derivatives against both methicillin-resistant and methicillin-sensitive Staphylococcus aureus suggests the compounds might find wide pharmaceutical use.

Anti-Bacterial Agents↗

Antibacterial activity of some Garcinia benzophenone derivatives against methicillin-resistant Staphylococcus aureus.

Benzophenone derivatives, garcinol (1) and isogarcinol (2) isolated from the pericarps of Garcinia purpurea (Guttiferae), and xanthochymol (3) and a mixture of isoxanthochymol (4) cycloxanthochymol (5) from the pericarps of G. subelliptica were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus. Among them, 3 showed the lowest minimum inhibitory concentration at 3.1-12.5 micrograms/ml. This concentration is nearly equal to that of the antibiotic, vancomycin.

Anti-Bacterial Agents↗