Magnitude Of Antibody Cross-Reactivity In Medically Important Mosquito-Borne Flaviviruses: A Systematic Review (Suburban Journal Club)
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Journal Article: Magnitude Of Antibody Cross-Reactivity In Medically Important Mosquito-Borne Flaviviruses: A Systematic Review
Journal: Infection and Drug Resistance, volume 14; pg no: 4291-4299
DOI: 10.2147/IDR.S336351
Flaviviruses are enveloped single-stranded RNA viruses belonging to the genus Flavivirus and family Flaviviridae. There are 53 recognized flavivirus spp., of which 40 are known to cause disease in humans.
The major human pathogenic viruses under this genera include:
- Dengue Virus (DENV)
- Japanese Encephalitis Virus (JEV)
- Zika Virus (ZIKV)
- Yellow Fever Virus (YFV)
- West Nile Virus (WNV)
Other viruses belonging to this genus may cause hemorrhagic fever and encephalitis.
These viruses are considered arboviruses, and are transmitted via mosquito bites. DENV alone infects >100 million people annually, and 500,000 people suffer from dengue fever.
While many flavivirus infections are asymptomatic, they may begin as an aspecific febrile illness and develop into a severe and life-threatening disease.
The flavivirus genome encodes three structural proteins required for the formation of virus particles:
- Capsid [C]
- Premembrane/membrane [prM/M]
- Envelope [E]
The genome also encodes 7 nonstructural (NS) proteins that are not part of infectious virus particles, but are critical for replication of viral RNA by suppressing antiviral defense responses mounted by the host after expression in infected cells:
- NS1
- NS2A
- NS2B
- NS3
- NS4A
- NS4B
- NS5
Cross-reaction of DENV with other flaviviruses:
| Target flavivirus | Cross-reaction with Abs produced against | Source of sample (serum) | Assay type | Cross-reaction (%) |
| DENV2 | YFV and/or JEV | JEV- and YFV-vaccinated | PRNT50 (titer at least 1:20) | 38.5 |
| DENV | JEV | JEV patients | PRNT50 (titer at least 1:10) | 15.4 |
| DENV1–4 | YFV and/or JEV | JEV patients immunized with YFV 17D vaccine | PRNT50 (titer at least 1:10) | 33.3 |
| DENV | YFV | YFV-vaccinated (17D vaccine) | IgG ELISA | 15.1 |
| DENV | TBEV | TBEV-vaccinated | IgG ELISA | 23.1 |
| DENV | ZIKV | ZIKV-infected travellers | DENV NS1 antigen ELISA | — |
| DENV | ZIKV | ZIKV-infected travellers | IgM ELISA | 31 |
| DENV | ZIKV | ZIKV-infected travellers | IgG ELISA | 54 |
| DENV | YFV | YFV patients | IgG ELISA | 76.9 |
| DENV | YFV | YFV patients | IgM ELISA | 46.2 |
| DENV | YFV | YFV vaccines | IgM ELISA | 42.1 |
| DENV | Non-dengue flaviviruses | YFV/WNV/JEV patients and TBEV vaccines | IgM IFA | 33 |
| DENV | Non-dengue flaviviruses | YFV/WNF/JEV patients and TBEV vaccines | IgG IFA | 71 |
| DENV | Non-dengue flaviviruses | YFV/WNF/JEV patients and TBEV vaccines | IgM EIA | 39 |
| DENV | Non-dengue flaviviruses | YFV/WNF/JEV patients and TBEV vaccines | IgG EIA | 84 |
| DENV | YFV | YFV vaccinated | IgG ELISA | 3.9 |
DENV – Dengue Virus; JEV – Japanese Encephalitis Virus; TBEV – Tick Borne Encephalitis Virus; WNV – West Nile Virus; YFV – Yellow fever Virus; ZIKV – Zika Virus
- Highest cross-reactions were observed between:
- DENV and YFY
- DENV and ZIKV
- The highest cross-reactivity was demonstrated with IgG-capture assays (ELISA/IFA/EIA) compared to IgM-capture assays (ELISA/IFA/EIA).
- Animal-model studies on closely related flaviviruses also demonstrated that IgG-based assays were less specific than IgM-based assays for homologous viruses.
- Assays based on the E protein compared to those based on the NS1 protein led to higher cross-reactivity
The full article with details about the cross-reactivity of other medically relevant flaviviruses can be accessed at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541746/
