Hemorrhagic Fever-Associated Faviviruses

Flaviviruses cause a broad spectrum of diseases, ranging from mild febrile symptoms to severe illnesses such as hemorrhagic fever, encephalitis, and congenital deformities. Creative Biolabs is dedicated to developing a series of anti-flaviviruses antibody including Dengue virus (DENV), Zika virus (ZIKV), Yellow fever virus (YFV), and West Nile virus.

Introduction of Flavivirus

Flaviviruses cause severe disease in humans worldwide, resulting in hundreds of millions of infections annually. Flavivirus is a genus of positive-strand RNA viruses in the family Flaviviridae. Flavivirus consists of more than 70 species and includes important and broadly distributed human pathogens, such as DENV, ZIKV, YFV, etc. Over 50% of known flaviviruses have been associated with human disease. There are two main groupings of viruses: those transmitted by ticks and those transmitted by mosquitoes. Mosquitoes are more closely associated with viscerotropic or hemorrhagic disease in humans while the tick-borne flaviviruses are typically associated with neurological symptoms although hemorrhagic manifestations have been documented. The hemorrhagic symptoms are mainly associated with DENV (mosquito-borne), YFV (mosquito-borne), ZIKV (mosquito-borne), Omsk hemorrhagic fever virus (OHFV, tick-borne), and Kyasanur forest disease virus (KFDV, tick-borne).

Flavivirus Structure and Morphogenesis

Flaviviruses are small, enveloped viruses with a single, positive-strand RNA genome of 10 to 12 kb. The surface of the flavivirus is composed of a shell made of 180 copies of both an envelope glycoprotein (E) and 1 of 2 other proteins anchored in a lipid membrane. The genomic RNA that contains a single open reading frame encodes three structural proteins (the capsid, precursor membrane (prM), and E protein) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5).

Fig.1 Flavivirus genome structure and virion. (Pierson, 2020)

Pathogenesis of Flavivirus

The hemorrhagic mechanism caused by Flaviviruses is not understood clearly, which may be associated with liver physiology, inflammatory cytokine response, or other mechanisms. Flaviviruses enter target cells by receptor-mediated endocytosis and traffic to endosomes. Flavivirus replication occurs on virus-induced host cell membranes. YFV directly infects hepatocytes and Kupffer cells leading to a loss of hepatocyte function and acute liver injury. YFV infection can also significantly impact the vascular endothelial cell barrier. It is not clear the exact mechanisms of the onset of vascular leakage. DENV infection of myeloid cells in blood and tissues is believed to induce an immunopathogenesis cascade resulting in vascular leakage, thrombocytopenia, abnormal bleeding, haemoconcentration, and hypotension.

Epidemiology

Flaviviruses have a global distribution. Approximately 400 million cases and 22 000 deaths occur due to dengue worldwide each year. YFV epidemic in Brazil is the largest in decades. In 2007, ZIKV was first detected outside of Asia and Africa, causing the first large outbreak ever reported. OHFV is found in a small region near Novosibirsk in Russia, KFDV is found in an ever-expanding range in India.

Fig.2 Global distribution of some Flaviviruses. (Pierson, 2020)

Prevention and Treatment

Flaviviral infection can be prevented by avoiding exposure to the arthropods that transmit these viruses. Some vaccines have been developed. YFV 17D, introduced in 1937, is a very effective and safe vaccine that was found to highly trigger the innate immune response to protect against YFV. At the current time, there are several vaccines that show promise, including CYD-TDV (or Dengvaxia) from Sanofi-Pasteur. A series of new ZIKV vaccine candidates are being developed and tested. There is no specific treatment for these illnesses. Supportive therapy may help reduce mortality.

What Creative Biolabs offers

Creative Biolabs has become a leader in antibody discovery, engineering, and manufacturing. Focused on ViroAntibody, we have developed numerous products targeting various viruses including Flaviviruses (DENV, ZIKV, and YFV). Customized antibody development services are also available for our clients. Please feel free to contact us for further information.

Reference

1. Pierson, T.C.; Diamond, M.S. The continued threat of emerging flaviviruses. Nat Microbiol. 2020, 5(6): 796-812.

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