Antigenic Relationships between Flaviviruses as Determined by Cross-neutralization Tests with Polyclonal Antisera

Calisher, Charles H.; Karabatsos, Nick; Dalrymple, Joel M.; Shope, Robert E.; Porterfield, J. S.; Westaway, E. G.; Brandt, Walter E.

doi:10.1099/0022-1317-70-1-37

Cited by 778 publications

(551 citation statements)

References 17 publications

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“…This relationship defines a super serogroup on the basis of strong crossneutralization through a conserved epitope that had not been recognized using polyclonal sera 8 . This finding thus introduces the possibility of developing a universal vaccine protecting against all the viruses from this group.…”

Section: Discussionmentioning

confidence: 99%

Structural basis of potent Zika–dengue virus antibody cross-neutralization

Barba-Spaeth

Dejnirattisai

Rouvinski

et al. 2016

Nature

479

540

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Zika virus (ZIKV) is an arthropod-borne enveloped virus belonging to the Flavivirus genus in the family Flaviviridae, which also includes the human pathogenic yellow fever, dengue, West Nile and tick-borne encephalitis viruses 1 . Flaviviruses have two structural glycoproteins, prM and E (for precursor membrane and envelope proteins, respectively), which form a heterodimer in the endoplasmic reticulum (ER) of the infected cell and drive the budding of spiky immature virions into the ER lumen. These particles transit through the cellular secretory pathway, during which the trans-Golgi-resident protease furin cleaves prM. This processing is required for infectivity, and results in the loss of a large fragment of prM and reorganization of E on the virion surface. The mature particles have a smooth aspect, with 90 E dimers organized with icosahedral symmetry in a 'herringbone' pattern 2,3 .Three-dimensional cryo-electron microscopy (cryo-EM) structures of the mature ZIKV particles have recently been reported to near atomic resolution (3.8 Å) 4,5 , showing that the virus has essentially the same organization as the other flaviviruses of known structure, such as dengue virus (DENV) 3 and West Nile virus 6,7 . The E protein is about 500 amino acids long, with the 400 N-terminal residues forming the ectodomain essentially folded as β-sheets with three domains, named I, II and III, aligned in a row with domain I at the centre. The conserved fusion loop is at the distal end of the rod in domain II, buried at the E dimer interface. At the C terminus, the E ectodomain is followed by the 'stem' , featuring two α-helices lying flat on the viral membrane (the stem helices), which link to two C-terminal transmembrane α-helices. The main distinguishing feature of the ZIKV virion is an insertion within a glycosylated loop of E (the '150' loop), which protrudes from the mature virion surface 4,5 .Flaviviruses have been grouped into serocomplexes based on cross-neutralization studies with polyclonal immune sera 8 . The E protein is the main target of neutralizing antibodies, and is also the viral fusogen; cleavage of prM allows E to respond to the endosomal pH by undergoing a large-scale conformational change that catalyses membrane fusion and releases the viral genome into the cyotosol. Loss of the precursor fragment of prM lets the E protein fluctuate from its tight packing at the surface of the virion, transiently exposing otherwise buried surfaces. One surface exposed by this 'breathing' is the fusionloop epitope (FLE), which is a dominant cross-reactive antigenic site 9 . Although antibodies to this site can protect by complement-mediated mechanisms, as shown in a mouse model for West Nile virus 10 , they are poorly neutralizing and lead to antibody-dependent enhancement 11-15 , thereby aggravating Flavivirus pathogenesis and complicating the development of safe and effective vaccines.We recently reported the functional and structural characterization of a panel of antibodies isolated from patients with dengue disease 13,16 . ...

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Section: Discussionmentioning

confidence: 99%

Structural basis of potent Zika–dengue virus antibody cross-neutralization

Barba-Spaeth

Dejnirattisai

Rouvinski

et al. 2016

Nature

479

540

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“…Flaviviruses including Entebbe bat virus (ENTV)[5,16], Bukalasa bat virus (BBV) and Dakar bat virus (DBV)[6,8], have been previously isolated from little free-tailed and Angolan free-tailed bats in Uganda, leaving open the possibility that some of the flavivirus antibody-positive bats in this study had been infected with one of those other viruses. We did not assess the serological cross-reactivity between ENTV, BBV, or DBV with the mosquito-borne viruses in our panel because they are classified in different antigenic complexes within the family Flaviviridae and therefore unlikely to cross-react serologically [17]. Egyptian rousette bats also displayed a relatively high flavivirus seroprevalence across all collections, with a total of 53/402 (13%) of Egyptian rousette bats exhibiting flavivirus neutralizing antibodies.…”

Section: Discussionmentioning

confidence: 99%

Neutralizing antibodies against flaviviruses, Babanki virus, and Rift Valley fever virus in Ugandan bats

Kading

Kityo

Mossel

et al. 2018

Infection Ecology & Epidemiology

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Introduction: A number of arboviruses have previously been isolated from naturally-infected East African bats, however the role of bats in arbovirus maintenance is poorly understood. The aim of this study was to investigate the exposure history of Ugandan bats to a panel of arboviruses. Materials and methods: Insectivorous and fruit bats were captured from multiple locations throughout Uganda during 2009 and 2011–2013. All serum samples were tested for neutralizing antibodies against West Nile virus (WNV), yellow fever virus (YFV), dengue 2 virus (DENV-2), Zika virus (ZIKV), Babanki virus (BBKV), and Rift Valley fever virus (RVFV) by plaque reduction neutralization test (PRNT). Sera from up to 626 bats were screened for antibodies against each virus. Results and Discussion: Key findings include the presence of neutralizing antibodies against RVFV in 5/52 (9.6%) of little epauletted fruit bats (Epomophorus labiatus) captured from Kawuku and 3/54 (5.6%) Egyptian rousette bats from Kasokero cave. Antibodies reactive to flaviviruses were widespread across bat taxa and sampling locations. Conclusion: The data presented demonstrate the widespread exposure of bats in Uganda to arboviruses, and highlight particular virus-bat associations that warrant further investigation.

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“…For the purposes of classification, a serogroup is defined as two or more viruses, distinct from each other by quantitative serologic standards (4-fold or greater difference between homologous and heterologous titers) in one or more tests, but related to each other or to other viruses by any serologic method. Viruses closely related within a serogroup but distinct from each other are considered to constitute an antigenic (11) and (82). b Viruses associated primarily with encephalitis syndrome.…”

Section: Introductionmentioning

confidence: 99%

Insect-transmitted vertebrate viruses: Flaviviridae

Ludwig

Iacono-Connors

1993

In Vitro Cell Dev Biol - Animal

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SUMMARYThe Flaviviridae include almost 70 viruses, nearly half of which have been associated with human disease. These viruses are among the most important arthropod-borne viruses worldwide and include dengue, yellow fever, and Japanese encephalitis viruses. Morbidity and mortality caused by these viruses vary, but collectively they account for millions of encephalitis, hemorrhagic fever, arthralgia, rash, and fever cases per year. Most of the members of this family are transmitted between vertebrate hosts by arthropod vectors, most commonly mosquitoes or ticks. Transmission cycles can be simple or complex depending on the hosts, vectors, the virus, and the environmental factors affecting both hosts and viruses. Replication of virus in invertebrate hosts does not seem to result in any significant pathology, which suggests a close evolutionary relationship between virus and vector. Another example of this relationship is the ability of these viruses to grow in invertebrate ceil culture, where replication usually results in a steady state, persistent infection, often without cytopathic effect. Yields of virus from insect cell culture vary but are generally similar to yields in vertebrate cells. Replication kinetics are comparable between insect and vertebrate ceil lines, despite differences in incubation temperature. Both vertebrate and insect cell culture systems continue to play a significant role in flavivirus isolation and the diagnosis of disease caused by these agents. Additionally, these culture systems permit the study of flavivirus attachment, penetration, replication, and release from cells and have been instrumental in the production and characterization of live-attenuated vaccines. Both vertebrate and insect cell culture systems will continue to play a significant role in basic and applied flavivirus research in the future.

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Antigenic Relationships between Flaviviruses as Determined by Cross-neutralization Tests with Polyclonal Antisera

Cited by 778 publications

References 17 publications

Structural basis of potent Zika–dengue virus antibody cross-neutralization

Structural basis of potent Zika–dengue virus antibody cross-neutralization

Neutralizing antibodies against flaviviruses, Babanki virus, and Rift Valley fever virus in Ugandan bats

Insect-transmitted vertebrate viruses: Flaviviridae

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