Enhancement of Zika virus infection by antibodies from West Nile virus seropositive individuals with no history of clinical infection

BMC Immunology - 2021
Himanshu Garg1, Rose Yeh2, Douglas M. Watts3, Tugba Mehmetoglu-Gurbuz1, Robert Resendes4, Bruce Parsons4, Fernando Gonzales4, Anjali Joshi1
1Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center, El Paso, USA
2Paul L Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, USA
3Department of Biological Sciences, University of Texas at El Paso, El Paso, USA
4Department of Public Health, City of El Paso, El Paso, USA

Tóm tắt

Abstract Background Recent outbreaks of Zika Virus (ZIKV) infection and associated microcephaly has raised multiple scientific questions. The close antigenic relatedness between flaviviruses makes diagnosis of specific infection difficult. This relatedness also raises the potential of Antibody Dependent Enhancement (ADE) via cross reactive antibodies to flaviviruses like West Nile Virus (WNV) and Dengue Virus (DENV). Asymptomatic WNV infections are endemic throughout the US creating a large proportion of the population that is seropositive for WNV antibodies. Whether these sero-positive individuals potentially carry ZIKV enhancing antibodies remains unknown. Results Serum samples obtained from human subjects with symptomatic or asymptomatic WNV infection from a WNV endemic region in Texas were tested for their ability to enhance or neutralize ZIKV infection. Sero-surveillance data demonstrated a ~ 7% prevalence for WNV antibodies in the population. Sera from both symptomatic and asymptomatic WNV seropositive donors effectively neutralized WNV and to some extent DENV infection. Interestingly, WNV+ sera failed to inhibit ZIKV while significantly enhancing infection. Conversely, ZIKV specific sera effectively neutralized ZIKV, with ADE only evident at lower concentrations. The enhancement of ZIKV via WNV antibody positive sera was likely due to non-neutralizing Envelope (E) antibodies as seen with monoclonal ZIKV E antibodies. Conclusions Overall, our findings suggest that WNV antibodies in the sera significantly enhance ZIKV infection in Fc receptor positive cells with limited neutralization activity. Further studies in more relevant models of ADE will be needed to confirm the relevance of these findings in vivo.

Từ khóa


Tài liệu tham khảo

Musso D, Gubler DJ. Zika Virus. Clin Microbiol Rev. 2016;29(3):487–524.

Dick GW, Kitchen SF, Haddow AJ. Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952;46(5):509–20.

Kindhauser MK, Allen T, Frank V, Santhana RS, Dye C. Zika: the origin and spread of a mosquito-borne virus. Bull World Health Organ. 2016;94(9):675–86C.

Fagbami AH. Zika virus infections in Nigeria: virological and seroepidemiological investigations in Oyo state. J Hyg (Lond). 1979;83(2):213–9.

Moore DL, Causey OR, Carey DE, Reddy S, Cooke AR, Akinkugbe FM, et al. Arthropod-borne viral infections of man in Nigeria, 1964-1970. Ann Trop Med Parasitol. 1975;69(1):49–64.

Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360(24):2536–43.

Blazquez AB, Saiz JC. Neurological manifestations of Zika virus infection. World J Virol. 2016;5(4):135–43..

Mlakar J, Korva M, Tul N, Popovic M, Poljsak-Prijatelj M, Mraz J, et al. Zika virus associated with microcephaly. N Engl J Med. 2016;374(10):951–8.

Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects--reviewing the evidence for causality. N Engl J Med. 2016;374(20):1981–7.

Cao-Lormeau VM, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J, et al. Guillain-Barre syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet. 2016;387(10027):1531–9.

Devhare P, Meyer K, Steele R, Ray RB, Ray R. Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells. Cell Death Dis. 2017;8(10):e3106.

Tang H, Hammack C, Ogden SC, Wen Z, Qian X, Li Y, et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell. 2016;18(5):587–90.

Carbaugh DL, Baric RS, Lazear HM. Envelope Protein Glycosylation Mediates Zika Virus Pathogenesis. J Virol. 2019;93(12):e00113–19.

Xia H, Luo H, Shan C, Muruato AE, Nunes BTD, Medeiros DBA, et al. An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction. Nat Commun. 2018;9(1):414.

Yuan L, Huang XY, Liu ZY, Zhang F, Zhu XL, Yu JY, et al. A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. Science. 2017;358(6365):933–6.

Mota MT, Terzian AC, Silva ML, Estofolete C, Nogueira ML. Mosquito-transmitted viruses - the great Brazilian challenge. Braz J Microbiol. 2016;47(Suppl 1):38–50.

Kuno G, Chang GJ, Tsuchiya KR, Karabatsos N, Cropp CB. Phylogeny of the genus Flavivirus. J Virol. 1998;72(1):73–83.

Halstead SB, Nimmannitya S, Cohen SN. Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered. Yale J Biol Med. 1970;42(5):311–28.

Kouri GP, Guzman MG, Bravo JR, Triana C. Dengue haemorrhagic fever/dengue shock syndrome: lessons from the Cuban epidemic, 1981. Bull World Health Organ. 1989;67(4):375–80.

Halstead SB, Russell PK. Protective and immunological behavior of chimeric yellow fever dengue vaccine. Vaccine. 2016;34(14):1643–7.

Petersen LR. Epidemiology of West Nile virus in the United States: implications for Arbovirology and public health. J Med Entomol. 2019;56(6):1456–62.

Roehrig JT, Layton M, Smith P, Campbell GL, Nasci R, Lanciotti RS. The emergence of West Nile virus in North America: ecology, epidemiology, and surveillance. Curr Top Microbiol Immunol. 2002;267:223–40.

Konishi E, Tabuchi Y, Yamanaka A. A simple assay system for infection-enhancing and -neutralizing antibodies to dengue type 2 virus using layers of semi-adherent K562 cells. J Virol Methods. 2010;163(2):360–7.

Smith SA, Nivarthi UK, de Alwis R, Kose N, Sapparapu G, Bombardi R, et al. Dengue virus prM-specific human monoclonal antibodies with virus replication-enhancing properties recognize a single Immunodominant antigenic site. J Virol. 2016;90(2):780–9.

Gould EA, Solomon T. Pathogenic flaviviruses. Lancet. 2008;371(9611):500–9.

de Oliveira WK, de Franca GVA, Carmo EH, Duncan BB, de Souza KR, Schmidt MI. Infection-related microcephaly after the 2015 and 2016 Zika virus outbreaks in Brazil: a surveillance-based analysis. Lancet. 2017;390(10097):861–70.

Petersen LR, Marfin AA. West Nile virus: a primer for the clinician. Ann Intern Med. 2002;137(3):173–9.

Li J, Loeb JA, Shy ME, Shah AK, Tselis AC, Kupski WJ, et al. Asymmetric flaccid paralysis: a neuromuscular presentation of West Nile virus infection. Ann Neurol. 2003;53(6):703–10.

Sejvar JJ, Haddad MB, Tierney BC, Campbell GL, Marfin AA, Van Gerpen JA, et al. Neurologic manifestations and outcome of West Nile virus infection. JAMA. 2003;290(4):511–5.

Colpitts TM, Conway MJ, Montgomery RR, Fikrig E. West Nile virus: biology, transmission, and human infection. Clin Microbiol Rev. 2012;25(4):635–48.

Gould LH, Fikrig E. West Nile virus: a growing concern? J Clin Invest. 2004;113(8):1102–7.

Murphy TD, Grandpre J, Novick SL, Seys SA, Harris RW, Musgrave K. West Nile virus infection among health-fair participants, Wyoming 2003: assessment of symptoms and risk factors. Vector Borne Zoonotic Dis. 2005;5(3):246–51.

Schweitzer BK, Kramer WL, Sambol AR, Meza JL, Hinrichs SH, Iwen PC. Geographic factors contributing to a high seroprevalence of West Nile virus-specific antibodies in humans following an epidemic. Clin Vaccine Immunol. 2006;13(3):314–8.

Kam YW, Lee CY, Teo TH, Howland SW, Amrun SN, Lum FM, et al. Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections. JCI Insight. 2017;2(8):e92428.

McCracken MK, Gromowski GD, Friberg HL, Lin X, Abbink P, De La Barrera R, et al. Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques. PLoS Pathog. 2017;13(8):e1006487.

Pantoja P, Perez-Guzman EX, Rodriguez IV, White LJ, Gonzalez O, Serrano C, et al. Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus. Nat Commun. 2017;8:15674.

Swanstrom JA, Plante JA, Plante KS, Young EF, McGowan E, Gallichotte EN, et al. Dengue Virus Envelope Dimer Epitope Monoclonal Antibodies Isolated from Dengue Patients Are Protective against Zika Virus. mBio. 2016;7(4):e01123–16.

Castanha PMS, Nascimento EJM, Braga C, Cordeiro MT, de Carvalho OV, de Mendonca LR, et al. Dengue virus-specific antibodies enhance Brazilian Zika virus infection. J Infect Dis. 2017;215(5):781–5.

Charles AS, Christofferson RC. Utility of a dengue-derived monoclonal antibody to enhance Zika infection in vitro. PLoS Curr. 2016;8.

Dejnirattisai W, Supasa P, Wongwiwat W, Rouvinski A, Barba-Spaeth G, Duangchinda T, et al. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus. Nat Immunol. 2016;17(9):1102–8.

Paul LM, Carlin ER, Jenkins MM, Tan AL, Barcellona CM, Nicholson CO, et al. Dengue virus antibodies enhance Zika virus infection. Clin Transl Immunology. 2016;5(12):e117.

Priyamvada L, Quicke KM, Hudson WH, Onlamoon N, Sewatanon J, Edupuganti S, et al. Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus. Proc Natl Acad Sci U S A. 2016;113(28):7852–7.

Slon Campos JL, Poggianella M, Marchese S, Mossenta M, Rana J, Arnoldi F, et al. DNA-immunisation with dengue virus E protein domains I/II, but not domain III, enhances Zika, West Nile and yellow fever virus infection. PLoS One. 2017;12(7):e0181734.

Langerak T, Mumtaz N, Tolk VI, van Gorp ECM, Martina BE, Rockx B, et al. The possible role of cross-reactive dengue virus antibodies in Zika virus pathogenesis. PLoS Pathog. 2019;15(4):e1007640.

Sariol CA, Nogueira ML, Vasilakis N. A tale of two viruses: does heterologous Flavivirus immunity enhance Zika disease? Trends Microbiol. 2018;26(3):186–90.

Bardina SV, Bunduc P, Tripathi S, Duehr J, Frere JJ, Brown JA, et al. Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity. Science. 2017;356(6334):175–80.

Calisher CH, Karabatsos N, Dalrymple JM, Shope RE, Porterfield JS, Westaway EG, et al. Antigenic relationships between flaviviruses as determined by cross-neutralization tests with polyclonal antisera. J Gen Virol. 1989;70(Pt 1):37–43.

Montecillo-Aguado MR, Montes-Gomez AE, Garcia-Cordero J, Corzo-Gomez J, Vivanco-Cid H, Mellado-Sanchez G, et al. Cross-reaction, enhancement, and neutralization activity of dengue virus antibodies against Zika virus: a study in the Mexican population. J Immunol Res. 2019;2019:7239347.

Garg H, Sedano M, Plata G, Punke EB, Joshi A. Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus. J Virol. 2017;91(20):e00834–17.

Pierson TC, Sanchez MD, Puffer BA, Ahmed AA, Geiss BJ, Valentine LE, et al. A rapid and quantitative assay for measuring antibody-mediated neutralization of West Nile virus infection. Virology. 2006;346(1):53–65.

Garg H, Lee RT, Tek NO, Maurer-Stroh S, Joshi A. Identification of conserved motifs in the West Nile virus envelope essential for particle secretion. BMC Microbiol. 2013;13:197.

Garg H, Mehmetoglu-Gurbuz T, Ruddy GM, Joshi A. Capsid containing virus like particle vaccine against Zika virus made from a stable cell line. Vaccine. 2019;37(48):7123–131.

Thông tin
Thông tin xuất bản

BMC Immunology

Thông tin tác giả