The Conserved Molecular Determinants of Virulence in Dengue Virus

Ahmad, Zuleeza; Poh, Chit Laa

doi:10.7150/ijms.29938

Cited by 17 publications

(14 citation statements)

References 104 publications

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“…The region of the DV-4 isolates that differed the most from AF326573 (the DV-4 standard strain) was in the NS2A and NS1 proteins (95.4% and 95.5% identity, respectively). However, amino acid changes in the motifs related to virulence and viability [ 24 , 25 ] were not observed in either DV-1 or DV-4 (Supplementary Tables S2 and S3).…”

Section: Resultsmentioning

confidence: 99%

Molecular evolution of dengue virus types 1 and 4 in Korean travelers

et al. 2021

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Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased worldwide, including in Korea, due to global warming and increased global travel. We therefore sought to characterize the molecular and evolutionary features of DV-1 and DV-4 isolated from Korean overseas travelers. We used phylogenetic analysis based on the full coding region to classify isolates of DV-1 in Korea into genotype I (43251, KP406802), genotype IV (KP406803), and genotype V (KP406801). In addition, we found that strains of DV-4 belonged to genotype I (KP406806) and genotype II (43257). Evidence of positive selection in DV-1 strains was identified in the C, prM, NS2A, and NS5 proteins, whereas DV-4 showed positive selection only in the non-structural proteins NS2A, NS3, and NS5. The substitution rates per site per year were 5.58 × 10-4 and 6.72 × 10-4 for DV-1 and DV-4, respectively, and the time of the most recent common ancestor was determined using the Bayesian skyline coalescent method. In this study, the molecular, phylogenetic, and evolutionary characteristics of Korean DV-1 and DV-4 isolates were evaluated for the first time.

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Section: Resultsmentioning

confidence: 99%

Molecular evolution of dengue virus types 1 and 4 in Korean travelers

et al. 2021

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“… 9 Chimeric tetravalent construct is composed of the live-attenuated yellow fever virus and DENV surface glycoproteins, but lacks nonstructural DENV proteins, with T-cell epitopes that may be essential to induce protective CMI responses against DENV. 19 Dengue-purified inactivated vaccine is a whole virus, purified, and inactivated vaccine, having potential advantages and disadvantages compared with live-attenuated vaccines with respect to their ability to induce anamnestic or CMI responses, or with respect to persistence of immunogenicity. As CYD-TDV, DPIV does not contain nonstructural DENV proteins.…”

Section: Discussionmentioning

confidence: 99%

Safety and Immunogenicity of an AS03B-Adjuvanted Inactivated Tetravalent Dengue Virus Vaccine Administered on Varying Schedules to Healthy U.S. Adults: A Phase 1/2 Randomized Study

Lin

Lyke

Koren

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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Dengue disease and its causative agents, the dengue viruses (DENV-1-4), cause high morbidity in tropical and subtropical regions. We evaluated three dosing regimens of the investigational tetravalent AS03 B-adjuvanted dengue-purified inactivated vaccine (DPIV+AS03 B). In this phase 1/2, observer-blind, placebo-controlled study (NCT02421367), 140 healthy adults were randomized 1:1:2 to receive DPIV+AS03 B according to the following regimens: 0-1 month (M), 0-1-6 M, or 0-3 M. Participants received DPIV+AS03 B or placebo at M0, M1, M3, and M6 according to their dosing schedule. Primary objectives were 1) to evaluate the safety of DPIV+AS03 B for 28 days (D) after each dose; 2) to demonstrate the added value of a booster dose (0-1-6 M versus 0-1 M) based on neutralizing antibody titers to each DENV type (DENV-1-4) at 28 D after the last dose; and, if this objective was met, 3) to demonstrate the benefit of a longer interval between the first and second doses (0-1 M versus 0-3 M). Adverse events (AEs) within 7 D after vaccination tended to be more frequent after DPIV+AS03 B doses than placebo; the number of grade 3 AEs was low (£ 4.5% after DPIV+AS03 B ; £ 2.9% after placebo), with no obvious differences across groups. Within 28 D following each dose, the frequency of unsolicited AEs after DPIV+AS03 B appeared higher for three-dose (0-1-6 M) than two-dose (0-1 M and 0-3 M) regimens. No serious AEs were considered related to vaccination, and no potential immune-mediated diseases were reported during the study. All three schedules were well tolerated. Both primary immunogenicity objectives were demonstrated. The 0-3 M and 0-1-6 M regimens were more immunogenic than the 0-1 M regimen.

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“…Much work [207] has been performed on Culex-borne JEV and WNV, Aedes-borne YFV and DENV, and tick-borne TBEV, while more limited datasets are available for other or recently emerging flaviviruses (ZIKV, for example). As a consequence, most of the molecular determinants shown to influence WNV, JEV, TBEV, MVEV, YFV, DENV, or ZIKV virulence or vector-borne transmission have only been studied for a single flavivirus [208,209]. Moreover, differences in the topology of NS proteins between flaviviruses, such as differences in NS2A aa residues exposed at the luminal side of the endoplasmic reticulum or in the cytoplasm of YFV and DENV infected cells, might explain, in part, the apparent variation in critical residues identified for different flaviviruses [210].…”

Section: A316mentioning

confidence: 99%

Molecular Determinants of West Nile Virus Virulence and Pathogenesis in Vertebrate and Invertebrate Hosts

Fiacre

Pagès

Albina

et al. 2020

IJMS

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West Nile virus (WNV), like the dengue virus (DENV) and yellow fever virus (YFV), are major arboviruses belonging to the Flavivirus genus. WNV is emerging or endemic in many countries around the world, affecting humans and other vertebrates. Since 1999, it has been considered to be a major public and veterinary health problem, causing diverse pathologies, ranging from a mild febrile state to severe neurological damage and death. WNV is transmitted in a bird–mosquito–bird cycle, and can occasionally infect humans and horses, both highly susceptible to the virus but considered dead-end hosts. Many studies have investigated the molecular determinants of WNV virulence, mainly with the ultimate objective of guiding vaccine development. Several vaccines are used in horses in different parts of the world, but there are no licensed WNV vaccines for humans, suggesting the need for greater understanding of the molecular determinants of virulence and antigenicity in different hosts. Owing to technical and economic considerations, WNV virulence factors have essentially been studied in rodent models, and the results cannot always be transported to mosquito vectors or to avian hosts. In this review, the known molecular determinants of WNV virulence, according to invertebrate (mosquitoes) or vertebrate hosts (mammalian and avian), are presented and discussed. This overview will highlight the differences and similarities found between WNV hosts and models, to provide a foundation for the prediction and anticipation of WNV re-emergence and its risk of global spread.

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The Conserved Molecular Determinants of Virulence in Dengue Virus

Cited by 17 publications

References 104 publications

Molecular evolution of dengue virus types 1 and 4 in Korean travelers

Molecular evolution of dengue virus types 1 and 4 in Korean travelers

Safety and Immunogenicity of an AS03B-Adjuvanted Inactivated Tetravalent Dengue Virus Vaccine Administered on Varying Schedules to Healthy U.S. Adults: A Phase 1/2 Randomized Study

Molecular Determinants of West Nile Virus Virulence and Pathogenesis in Vertebrate and Invertebrate Hosts

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