Immature Dengue Virus: A Veiled Pathogen?

English version České info

Cells infected with dengue virus release a high proportion of immature prM-containing virions. In accordance, substantial levels of prM antibodies are found in sera of infected humans. Furthermore, it has been recently described that the rates of prM antibody responses are significantly higher in patients with secondary infection compared to those with primary infection. This suggests that immature dengue virus may play a role in disease pathogenesis. Interestingly, however, numerous functional studies have revealed that immature particles lack the ability to infect cells. In this report, we show that fully immature dengue particles become highly infectious upon interaction with prM antibodies. We demonstrate that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells. In addition, enzymatic activity of furin is critical to render the internalized immature virus infectious. Together, these data suggest that during a secondary infection or primary infection of infants born to dengue-immune mothers, immature particles have the potential to be highly infectious and hence may contribute to the development of severe disease.

Vyšlo v časopise: Immature Dengue Virus: A Veiled Pathogen?. PLoS Pathog 6(1): e32767. doi:10.1371/journal.ppat.1000718
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000718

Souhrn

Zdroje

1. HalsteadSB

1970 Observations related to pathogenesis of dengue hemorrhagic fever. VI. Hypotheses and discussion. Yale J Biol Med 42 350 362

2. HalsteadSB

1988 Pathogenesis of dengue: challenges to molecular biology. Science 239 476 481

3. VaughnDW

GreenS

KalayanaroojS

InnisBL

NimmannityaS

2000 Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 181 2 9

4. HalsteadSB

LanNT

MyintTT

ShweTN

NisalakA

2002 Dengue hemorrhagic fever in infants: research opportunities ignored. Emerg Infect Dis 8 1474 1479

5. KliksSC

NimmanityaS

NisalakA

BurkeDS

1988 Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 38 411 419

6. HalsteadSB

2003 Neutralization and antibody-dependent enhancement of dengue viruses. Adv Virus Res 60 421 467

7. KliksSC

NisalakA

BrandtWE

WahlL

BurkeDS

1989 Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Am J Trop Med Hyg 40 444 451

8. LibratyDH

YoungPR

PickeringD

EndyTP

KalayanaroojS

2002 High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis 186 1165 1168

9. LibratyDH

EndyTP

HoungHS

GreenS

KalayanaroojS

2002 Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections. J Infect Dis 185 1213 1221

10. WangWK

ChaoDY

KaoCL

WuHC

LiuYC

2003 High levels of plasma dengue viral load during defervescence in patients with dengue hemorrhagic fever: implications for pathogenesis. Virology 305 330 338

11. WangWK

ChenHL

YangCF

HsiehSC

JuanCC

2006 Slower rates of clearance of viral load and virus-containing immune complexes in patients with dengue hemorrhagic fever. Clin Infect Dis 43 1023 1030

12. van der SchaarHM

RustMJ

ChenC

vandE-M

WilschutJ

2008 Dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells. PLoS Pathog 4 e1000244 doi:10.1371/journal.ppat.1000244

13. MackenzieJM

WestawayEG

2001 Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J Virol 75 10787 10799

14. YuIM

ZhangW

HoldawayHA

LiL

KostyuchenkoVA

2008 Structure of the immature dengue virus at low pH primes proteolytic maturation. Science 319 1834 1837

15. van der SchaarHM

RustMJ

WaartsBL

vandE-M

KuhnRJ

2007 Characterization of the early events in dengue virus cell entry by biochemical assays and single-virus tracking. J Virol 81 12019 12028

16. ZybertIA

vandE-M

WilschutJ

SmitJM

2008 Functional importance of dengue virus maturation: infectious properties of immature virions. J Gen Virol 89 3047 3051

17. CherrierMV

KaufmannB

NybakkenGE

LokSM

WarrenJT

2009 Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody. EMBO J 28 3269 3276

18. ElshuberS

AllisonSL

HeinzFX

MandlCW

2003 Cleavage of protein prM is necessary for infection of BHK-21 cells by tick-borne encephalitis virus. J Gen Virol 84 183 191

19. ElshuberS

MandlCW

2005 Resuscitating mutations in a furin cleavage-deficient mutant of the flavivirus tick-borne encephalitis virus. J Virol 79 11813 11823

20. GuirakhooF

BolinRA

RoehrigJT

1992 The Murray Valley encephalitis virus prM protein confers acid resistance to virus particles and alters the expression of epitopes within the R2 domain of E glycoprotein. Virology 191 921 931

21. HeinzFX

StiasnyK

Puschner-AuerG

HolzmannH

AllisonSL

1994 Structural changes and functional control of the tick-borne encephalitis virus glycoprotein E by the heterodimeric association with protein prM. Virology 198 109 117

22. StadlerK

AllisonSL

SchalichJ

HeinzFX

1997 Proteolytic activation of tick-borne encephalitis virus by furin. J Virol 71 8475 8481

23. LaiCY

TsaiWY

LinSR

KaoCL

HuHP

2008 Antibodies to envelope glycoprotein of dengue virus during the natural course of infection are predominantly cross-reactive and recognize epitopes containing highly conserved residues at the fusion loop of domain II. J Virol 82 6631 6643

24. HuangKJ

YangYC

linYS

liuHS

YehTM

2005 Flow Cytometric Determination for Dengue Virus-Infected cells: Its application for Antibody-Dependent Enhancement study. Dengue Bulletin 29 142 150

25. HuangKJ

YangYC

LinYS

HuangJH

LiuHS

2006 The dual-specific binding of dengue virus and target cells for the antibody-dependent enhancement of dengue virus infection. J Immunol 176 2825 2832

26. RandolphVB

WinklerG

StollarV

1990 Acidotropic amines inhibit proteolytic processing of flavivirus prM protein. Virology 174 450 458

27. HuangKJ

linYS

HuangJH

liuHS

YehTM

2008 Anti-prM Antibody as an Autoantibody in Dengue Virus Infection. American Journal of Infectious Diseases 4 59 67

28. FalconarAK

1999 Identification of an epitope on the dengue virus membrane (M) protein defined by cross-protective monoclonal antibodies: design of an improved epitope sequence based on common determinants present in both envelope (E and M) proteins. Arch Virol 144 2313 2330

29. GartenW

HallenbergerS

OrtmannD

SchaferW

VeyM

1994 Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones. Biochimie 76 217 225

30. HalsteadSB

2007 Dengue. Lancet 370 1644 1652

31. BrandtWE

McCownJM

GentryMK

RussellPK

1982 Infection enhancement of dengue type 2 virus in the U-937 human monocyte cell line by antibodies to flavivirus cross-reactive determinants. Infect Immun 36 1036 1041

32. GoncalvezAP

EngleRE

StCM

PurcellRH

LaiCJ

2007 Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention. Proc Natl Acad Sci U S A 104 9422 9427

33. ZhangY

CorverJ

ChipmanPR

ZhangW

PletnevSV

2003 Structures of immature flavivirus particles. EMBO J 22 2604 2613

34. ZhangX

FugereM

DayR

KielianM

2003 Furin processing and proteolytic activation of Semliki Forest virus. J Virol 77 2981 2989

35. KinneyRM

ButrapetS

ChangGJ

TsuchiyaKR

RoehrigJT

1997 Construction of infectious cDNA clones for dengue 2 virus: strain 16681 and its attenuated vaccine derivative, strain PDK-53. Virology 230 300 308

36. DiamondMS

EdgilD

RobertsTG

LuB

HarrisE

2000 Infection of human cells by dengue virus is modulated by different cell types and viral strains. J Virol 74 7814 7823