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Related post: n (b) Human tissues H Cataflam D (c) Neither SUMMARY OF WORK (Use standard unreduced type. Do not exceed the space provided.) TERMINATED 1991-92 10-60 PHS 6040 (Rev. 1/84) us GOVERNUEHTPflMTNG OFFICE: 1B1 O-aW-tU DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBUC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER ZOl AI 00500-06 LID PERIOD COVERED October 1, 1991 to September 30, 1992 Tm.E OF PROJECT (80 characters or less. TiOe must lit on one line between the tiorders.) Processing and Immunogenicity of Dengue Type 4 Virus Nonstructural Protein NS 1 PRINCIPAL INVESTIGATOR (Ust other protessional personnel below the Principal Investigator.) (Name, title, laboratory, and instllute affiliation) PI: Ching-Juh Lai, Ph.D. Head, MVB Section LID, NIAID Others: Barry Falgout, Ph.D. Lewis Markoff, M.D. Senior Staff Fellow Medical Officer LID, NIAID LID, NIAID COOPERATING UNITS (if any) LAB/BRANCH Laboratory of Infectious Diseases SECTION Molecular Viral Biology Section INSTfTUTE AND LOCATION NIAID, NTH, Bethesda, MD 20892 TOTAL MAN- YEARS: 0.5 PROFESSIONAL: 0.5 CHECK APPROPRIATE BOX(ES) n (a) Human subjects n (a1) Minors D (a2) Interviews n (b) Human tissues (c) Neither SUMMARY OF WORK (Use standard unreduced type. Do not exceed the space provided.) Previous results from our laboratory established that the N-terminal 70% of NS2A and the C-terminal 8 amino acids of NSl are required for NS1-NS2A cleavage. To further delineate the requirements for Cataflam Novartis NS1-NS2A cleavage, we constructed recombinant vaccinia viruses expressing chimeric proteins consisting of PreM fused to the 3 or 8 C-terminal amino acids of NS Novartis Cataflam 1 plus NS2A. The results showed that all of NSl, with the exception of the 8 amino acid cleavage site, is dispensable for NS1-NS2A cleavage. Also, a signal sequence is required for cleavage to occur as the chimeric protein SigPreM-NSl(8)-NS2A was not cleaved. This suggests that targeting to the exocytic pathway is a prerequisite for NS1-NS2A cleavage. Additional experiments were Cataflam 50mg performed to analyze this cleavage. Brefeldin A, a drug which blocks transport out of the Golgi, did not block NS1/NS2A Cataflam Tablets cleavage. This suggests that NS1/NS2A cleavage occurs in the Golgi or in Cataflam 50 Mg a compartment between the ER and the Golgi. NS1/NS2A cleavage was studied during a chase under conditions that block ER-to-Golgi transport: incubation with the drug carbonyl cyanide m- chlorophenylhydrazone (CCCP), or incubation at 14°C. Both of these treatments completely blocked the chase of uncleaved NS1-NS2A precursor into NSl product. This is consistent with Cataflam 25mg the notion that NS1/NS2A cleavage occurs after exit from the ER. Further elucidation Cataflam Diclofenac of the cleavage mechanism is now possible using an in vitro ER-to-Golgi transport system recently developed by others. 10-61 PHS 6040 (Rev. 1/84) U.S.GOVB«UCNTI>RMTMGCFFICE: tw O-ttMU DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBUC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER ZOl AI 00501-05 LID PERIOD COVERED October 1, 1991 to September 30, 1992 TITLE OF PROJECT (80 characters or less. TiUe must Tit on one lirte between the borders.) Study of the Processing of Dengue Viral Glycoproteins PRINCIPAL INVESTIGATOR Buy Cataflam (List other prolessional personnel below the Principal Investigator.) (Name, title, laboratory, and institute afTiHatlon) PI: Lewis J. Markoff, M.D. Medical Officer LID, NIAID COOPERATING UNITS (ilany) LAB/BRANCH Laboratory of Infectious Diseases SECTION Molecular Viral Biology Section INSTFTUTE AND LOCATION NIAID, NIH, Bethesda, MD 20892 TOTAL MAN- YEARS; PROFESSIONAL: CHECK APPROPRIATE BOX(ES) n (a) Human subjects D (a1) Minors D (a2) Interviews n (b) Human tissues S (c) Neither SUMMARY OF WOFIK (Use standard unreduced type. Do not exceed the space provided.) TERMINATED 1991-92 10-62 PHS 6040 (Rev. 1/84) USLGOVSMCNTPRMrMGOmCE: ian04(MH DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBUC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER
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