Introduction of mutations into the non-structural genes or 3′ untranslated region of an attenuated dengue virus type 4 vaccine candidate further decreases replication in rhesus monkeys while retaining protective immunity

Vaccine ◽  
2004 ◽  
Vol 22 (25-26) ◽  
pp. 3440-3448 ◽  
Author(s):  
Kathryn A Hanley ◽  
Luella R Manlucu ◽  
Gracielle G Manipon ◽  
Christopher T Hanson ◽  
Stephen S Whitehead ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Rhesus Monkeys ◽  
Untranslated Region ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Structural Genes

scholarly journals A Live, Attenuated Dengue Virus Type 1 Vaccine Candidate with a 30-Nucleotide Deletion in the 3′ Untranslated Region Is Highly Attenuated and Immunogenic in Monkeys

2003 ◽  
Vol 77 (2) ◽  
pp. 1653-1657 ◽  
Author(s):  
Stephen S. Whitehead ◽  
Barry Falgout ◽  
Kathryn A. Hanley ◽  
Joseph E. Blaney, ◽  
Lewis Markoff ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Rhesus Monkeys ◽  
Untranslated Region ◽  
Vaccine Candidate ◽  
Homologous Region ◽  
Wild Type ◽  
Nucleotide Deletion ◽  
Intrathoracic Inoculation

ABSTRACT The Δ30 deletion mutation, which was originally created in dengue virus type 4 (DEN4) by the removal of nucleotides 172 to 143 from the 3′ untranslated region (3′ UTR), was introduced into a homologous region of wild-type (wt) dengue virus type 1 (DEN1). The resulting virus, rDEN1Δ30, was attenuated in rhesus monkeys to a level similar to that of the rDEN4Δ30 vaccine candidate. rDEN1Δ30 was more attenuated in rhesus monkeys than the previously described vaccine candidate, rDEN1mutF, which also contains mutations in the 3′ UTR, and both vaccines were highly protective against challenge with wt DEN1. Both rDEN1Δ30 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However, neither rDEN1Δ30 nor rDEN1mutF showed restricted replication following intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability of the Δ30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a tetravalent DEN vaccine could be generated by introduction of the Δ30 mutation into wt DEN viruses belonging to each of the four serotypes.

scholarly journals PERAN GEN STRUKTURAL, GEN NON-STRUKTURAL, DAN UNTRANSLATED REGION DALAM PERAKITAN VIRUS DENGUE

2015 ◽  
Vol 7 (2) ◽  
Author(s):  
Meiranty C. Pangerapan ◽  
Beivy J. Kolondam
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Aedes Albopictus ◽  
Untranslated Region ◽  
Rna Virus ◽  
Virus Genome ◽  
Interferon Response ◽  
Endoplasmic Reticulum Membrane ◽  
Structural Genes

Abstract: Dengue virus is a single-stranded RNA virus that belongs to Flaviviridae family. This virus causes dengue fever which is transmitted by Aedes aegypti dan Aedes albopictus. There are four serotypes of dengue virus; all of them can cause dengue fever. Understanding the genomics of dengue virus is important for research and diagnostics. The genome of dengue virus is 11 kilo-base long. It consists of 5’-untranslated region (5’-UTR), three structural genes (coding capsid protein, pre-membrane/membrane, and envelope), seven non-structural genes (coding NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 proteins) and 3’-UTR. Non-structural genes are encoding proteins of viral RNA replication, interferon response, viral assembly and secretion, endoplasmic reticulum membrane invagination induction, immune-mediator induction, and RNA 5’-caping.Keywords: dengue virus, genome, structural genes, non-structural genes, untranslated region.Abstrak: Virus dengue merupakan virus RNA beruntai tunggal yang termasuk dalam famili Flaviviridae. Virus ini adalah penyebab penyakit demam berdarah dengue yang ditransmisikan melalui nyamuk Aedes aegypti dan Aedes albopictus. Ada empat serotipe virus dengue yang telah dikenal secara luas yang ada semuanya dapat menimbulkan penyakit demam berdarah. Pemahaman tentang genomik virus dengue sangat penting untuk pengembangan penelitian dan juga untuk keperluan diagnostik. Genom virus dengue memiliki panjang 11 kilo basa. Genomnya tersusun atas 5’-untranslated region (5’-UTR), tiga gen struktural (mengodekan protein kapsid, premembran/membran dan amplop), tujuh gen non-struktural (mengodekan protein NS1, NS2A, NS2B, NS3, NS4A, NS4B dan NS5) dan 3’-UTR. Gen-gen non-struktural mengodekan protein untuk replikasi RNA virus, respon interferon, perakitan, sekresi partikel virus, menginduksi invaginasi membran retikulum endoplasma, induksi imunomediator dan penambahan tudung pada ujung 5’ RNA.Kata kunci: virus dengue, genom, gen struktural, gen non-struktural, untranslated region

scholarly journals Vaccine candidates for dengue virus type 1 (DEN1) generated by replacement of the structural genes of rDEN4 and rDEN4Δ30 with those of DEN1

2007 ◽  
Vol 4 (1) ◽  
Author(s):  
Joseph E Blaney ◽  
Neeraj S Sathe ◽  
Christopher T Hanson ◽  
Cai Yen Firestone ◽  
Brian R Murphy ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Structural Genes ◽  
Vaccine Candidates

scholarly journals rDEN4Δ30, a Live Attenuated Dengue Virus Type 4 Vaccine Candidate, Is Safe, Immunogenic, and Highly Infectious in Healthy Adult Volunteers

2005 ◽  
Vol 191 (5) ◽  
pp. 710-718 ◽  
Author(s):  
Anna P. Durbin ◽  
Stephen S. Whitehead ◽  
Julie McArthur ◽  
John R. Perreault ◽  
Joseph E. Blaney, Jr. ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Healthy Adult ◽  
Vaccine Candidate ◽  
Adult Volunteers

scholarly journals Phase 1 Trial of the Dengue Virus Type 4 Vaccine Candidate rDEN4Δ30-4995 in Healthy Adult Volunteers

2009 ◽  
Vol 81 (5) ◽  
pp. 834-841 ◽  
Author(s):  
Peter F. Wright ◽  
Anna P. Durbin ◽  
Bhavin Thumar ◽  
Brett A. McKinney ◽  
Joseph E. Blaney ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Healthy Adult ◽  
Vaccine Candidate ◽  
Phase 1 ◽  
Phase 1 Trial ◽  
Adult Volunteers
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