Autographa californica multiple nucleopolyhedrovirus orf132 encodes a nucleocapsid-associated protein required for budded-virus and multiply enveloped occlusion-derived virus production.

UNLABELLED: Autographa californica multiple nucleopolyhedrovirus orf132 (named ac132) has homologs in all genome-sequenced group I nucleopolyhedroviruses. Its role in the viral replication cycle is unknown. In this study, ac132 was shown to express a protein of around 28 kDa, which was determined to be associated with the nucleocapsids of both occlusion-derived virus and budded virus. Confocal microscopy showed that AC132 protein appeared in central region of the nucleus as early as 12 h postinfection with the virus. It formed a ring zone at the periphery of the nucleus by 24 h postinfection. To investigate its role in virus replication, ac132 was deleted from the viral genome by using a bacmid system. In the Sf9 cell culture transfected by the ac132 knockout bacmid, infection was restricted to single cells, and the titer of infectious budded virus was reduced to an undetectable level. However, viral DNA replication and the expression of late genes vp39 and odv-e25 and a reporter gene under the control of the very late gene p10 promoter were unaffected. Electron microscopy showed that nucleocapsids, virions, and occlusion bodies were synthesized in the cells transfected by an ac132 knockout bacmid, but the formation of the virogenic stroma and occlusion bodies was delayed, the numbers of enveloped nucleocapsids were reduced, and the occlusion bodies contained mainly singly enveloped nucleocapsids. AC132 was found to interact with envelope protein ODV-E18 and the viral DNA-binding protein P6.9. The data from this study suggest that ac132 possibly plays an important role in the assembly and envelopment of nucleocapsids. IMPORTANCE: To our knowledge, this is the first report on a functional analysis of ac132. The data presented here demonstrate that ac132 is required for production of the budded virus and multiply enveloped occlusion-derived virus of Autographa californica multiple nucleopolyhedrovirus. This article reveals unique phenotypic changes induced by ac132 deletion on the virus and multiple new findings on ac132.

[Therapeutic effects of FOLFOX6 versus TLF regimen as the first line chemotherapy for advanced gastric cancer].

OBJECTIVE: To compare the efficacy, time to disease progression (TTP), overall survival (OS) and toxicity of FOLFOX6 and TLF regimens for advanced gastric cancer. METHODS: The clinical data of 81 chemotherapy-naive patients with advanced gastric cancer were analyzed. Of the 81 patients, 41 were treated with FOLFOX6 regimen and 40 with TLF regimen. The patients in FOLFOX6 group received intravenous infusion of L-OHP(100 mg/m2) at day 1, bolus injection of 5-FU (400 mg/m2) at day 1, and continuous intravenous infusion of 5-FU (1200 mg/m2/d) for 22 h at days 1-2, each treatment cycle lasting 14 days. The patients in TCF group received TAX (90 mg/m2) at day 1, bolus injection of 5-FU (400 mg/m2) at days 1-2, and continuous intravenous infusion of 5-FU (400 mg/m2/d) for 22 h at days 1-2, and each treatment cycle also lasted 14 days. RESULTS: The objective response rates were 48.8% in FOLFOX6 group and 50.0% in TLF group (P=0.962). The median TTP in the two groups was 6.30 months and 6.50 months (P=0.958), with median survival time of 9.80 months and 10.70 months (P=0.578), respectively. The most frequent adverse events were nausea, vomiting and hematologic toxicities. The incidences of grade III-IV leucopenia and neutropenia were lower in FOLFOX6 group than in TLF group, but the difference was not statistically significant (12.2% vs 30.0%, P=0.112; 14.6% vs 32.5%, P=0.126). Three patients in FOLFOX6 group developed intestinal obstruction during the chemotherapy. CONCLUSION: Both FOLFOX6 and TLF regimens are effective in treating advanced gastric cancer and the toxicities can be tolerated.