Phylogenesys and homology modeling in Zika virus epidemic: food for thought.
Zika virus (ZIKV) is an emerging Flavivirus that have recently caused an outbreak in Brazil and rapid spread in several countries. In this study, the consequences of ZIKV evolution on protein recognition by the host immune system have been analyzed. Evolutionary analysis was combined with homology modeling and T-B cells epitope predictions. Two separate clades, the African one with the Uganda sequence, as the most probable ancestor, and the second one containing all the most recent sequences from the equatorial belt were identified. Brazilian strains clustered all together and closely related to the French Polynesia isolates. A strong presence of a negatively selected site in the envelope gene (Env) protein was evidenced, suggesting a probable purging of deleterious polymorphisms in functionally important genes. Our results show relative conservancy of ZIKV sequences when envelope and other non-structural proteins (NS3 and NS5) are analyzed by homology modeling. However, some regions within the consensus sequence of NS5 protein and to a lesser extent in the envelope protein, show localized high mutation frequency corresponding to a considerable alteration in protein stability. In terms of viral immune escape, envelope protein is under a higher selective pressure than NS5 and NS3 proteins for HLA class I and II molecules. Moreover, envelope mutations that are not strictly related to T-cell immune responses are mostly located on the surface of the protein in putative B-cell epitopes, suggesting an important contribution of B cells in the immune response as well.
a Unit of Clinical Pathology and Microbiology , University Campus Bio-Medico , Rome , Italy.
Silvia
S
Angeletti
b Department of Infectious, Parasitic, and Immune-Mediated Diseases, Epidemiology Unit, Reference Centre on Phylogeny, Molecular Epidemiology, and Microbial Evolution (FEMEM) , National Institute of Health , Rome , Italy.
Alessandra
A
Lo Presti
c Oswaldo Cruz Foundation (FIOCRUZ) , Salvador , Brazil.|d Department of Biology , University of Rome 'Tor Vergata' , Rome , Italy.
Marta
M
Giovanetti
e ProxAgen Ltd , Sofia , Bulgaria.
Alba
A
Grifoni
e ProxAgen Ltd , Sofia , Bulgaria.|f Department of Biomedicine and Prevention , University of Rome "Tor Vergata" , Rome , Italy.
Massimo
M
Amicosante
g Laboratory of Molecular Virology , Polyclinic Tor Vergata Foundation , Rome , Italy.
Marco
M
Ciotti
c Oswaldo Cruz Foundation (FIOCRUZ) , Salvador , Brazil.
Luiz-Carlos J
LJ
Alcantara
b Department of Infectious, Parasitic, and Immune-Mediated Diseases, Epidemiology Unit, Reference Centre on Phylogeny, Molecular Epidemiology, and Microbial Evolution (FEMEM) , National Institute of Health , Rome , Italy.|h Department of Public Health and Infectious Diseases , Sapienza University of Rome , Rome , Italy.
Eleonora
E
Cella
a Unit of Clinical Pathology and Microbiology , University Campus Bio-Medico , Rome , Italy.|b Department of Infectious, Parasitic, and Immune-Mediated Diseases, Epidemiology Unit, Reference Centre on Phylogeny, Molecular Epidemiology, and Microbial Evolution (FEMEM) , National Institute of Health , Rome , Italy.
Massimo
M
Ciccozzi
D001402:B-Lymphocytes / Q000276:immunology; D016384:Consensus Sequence; D058872:Epidemics; D000939:Epitopes / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D010802:Phylogeny; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D000071244:Zika Virus / Q000145:classification / Q000235:genetics* / Q000276:immunology; D000071243:Zika Virus Infection / Q000453:epidemiology* / Q000517:prevention & control / Q000821:virology
D000939:Epitopes; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins
Evolutionary analysis; Homology modeling; T-B cells epitope predictions; Zika
BMC Bioinformatics. 2007 Jul 04;8:238
17608956
Bioinformatics. 2011 Jun 15;27(12):1711-2
21505037
Nat Protoc. 2009;4(3):363-71
19247286
Vector Borne Zoonotic Dis. 2016 Feb;16(2):75-6
26824625
Microbes Infect. 2016 Mar;18(3):163-6
26706817
Viruses. 2011 Dec;3(12):2374-95
22355444
J Gen Virol. 2016 Feb;97(2):269-73
26684466
Genetics. 1998 Mar;148(3):929-36
9539414
Microbes Infect. 2016 Mar;18(3):167-8
26774330
Proc Natl Acad Sci U S A. 2013 May 28;110(22):E2046-53
23580623
Sci Rep. 2015 May 14;5:10170
25973685
BMC Bioinformatics. 2005 May 31;6:132
15927070
MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3
26796813
AIDS Res Hum Retroviruses. 2011 Aug;27(8):921-4
21114462
J Clin Virol. 2016 Jan;74:1-3
26615388
Emerg Infect Dis. 2015 Oct;21(10):1885-6
26401719
Antivir Chem Chemother. 2015 Aug;24(3-4):118-26
27296393
Bioinformatics. 2005 Mar 1;21(5):676-9
15509596
Infect Genet Evol. 2012 Mar;12(2):392-8
22244786
Immunology. 2012 Oct;137(2):117-23
22681406
Am J Public Health. 2016 Apr;106(4):589-90
26959253
Immunogenetics. 2005 Jun;57(5):304-14
15868141
Lancet. 2016 Jan 16;387(10015):228
26775125
Nat Biotechnol. 1999 Jun;17(6):555-61
10385319
Viral Immunol. 2016 Sep;29(7):436-43
27438351
PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636
24421913
J Infect Dev Ctries. 2015 Jul 04;9(6):684-5
26142684
Protein Sci. 2003 May;12(5):1007-17
12717023
Mol Biol Evol. 2005 May;22(5):1208-22
15703242