Order Martellivirales: Togaviridae
Paul Pumpens, Peter Pushko, Philippe Le Mercier in Virus-Like Particles, 2022
Garg et al. (2020) generated a universal VLP vaccine termed CJaYZ targeting not only CHIKV but also Japanese encephalitis (JEV), yellow fever (YFV), and Zika (ZIKV) viruses from the Flaviviridae family, order Amarillovirales (see Chapter 22). For CHIKV, the vaccine included C-E3-E2-E1 genes. The stable 293T cell lines secreting VLPs containing capsid protein for all four viruses were established and adapted to grow in suspension cultures to facilitate vaccine scale up. The immunization of mice with different combinations of the capsid protein containing VLPs either as monovalent, bivalent, or tetravalent formulation resulted in generation of high levels of neutralizing antibodies. The potential tetravalent VLP vaccine candidate provided strong neutralizing antibody titers against all four viruses (Garg et al. 2020).
Yellow Fever
Rae-Ellen W. Kavey, Allison B. Kavey in Viral Pandemics, 2020
The family Flaviviridae contains three genera: the above-described flaviviruses, which include yellow fever virus (YFV), West Nile virus (WNV), dengue virus (DENV) and Zika virus (ZIKV); the hepaci-viruses, which include hepatitis B and C viruses; and the pesti-viruses, which infect hoofed mammals. The vector-borne arboviruses are grouped as a clade within the Flavivirus genus and this is subdivided into a mosquito-borne clade and a tick-borne clade. The mosquito clade is divided into two branches: one branch contains the neurotropic viruses, often associated with encephalitic disease in humans or livestock. This branch tends to be spread by the Culex mosquito species and to have bird reservoirs – an example is the West Nile virus. The second branch is the group associated with hemorrhagic disease in humans. These tend to have Aedes species as vectors and primate hosts – the yellow fever virus is emblematic of this group.46
Arthropod-borne virus encephalitis
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Phylogenetic studies of the flaviviruses, an arbovirus genus of the family Flaviviridae, suggest that they may have evolved first as non-vector-borne viral clusters, and that tick-borne and mosquito-borne viral clusters evolved subsequently [5]. Based on physical-chemical relationships, the arboviruses fall into six families, of which three contain particularly important agents causing encephalitis (Table 16.1). All three contain single stranded RNA viruses, ranging in size from 40 to 60 nm of the Flaviviridae family to 80–120 nm of the Bunyaviridae. Alpha and flaviviruses contain one RNA molecule of about 10–12 kDA whereas the genome of viruses of the family Bunyaviridae family consists of three segments of RNA.
An update on dengue vaccine development, challenges, and future perspectives
Published in Expert Opinion on Drug Discovery, 2021
Fakhriedzwan Idris, Donald Heng Rong Ting, Sylvie Alonso
A number of hypotheses that involve both viral and host factors have been proposed to explain dengue pathogenesis and have been reviewed in detail elsewhere [7,8]. Severe cases have been associated with secondary heterologous infections, and this was proposed to be due to the presence of antibodies produced during the primary DENV infection that bind to but do not neutralize the heterologous DENV, and facilitate entry inside FcγR-expressing permissive cells, leading to increased viral loads and enhanced disease severity, a term coined antibody-dependent enhancement (ADE) [3]. Presence of IgG antibodies specific to Japanese encephalitis virus, another member of the Flaviviridae family, was also proposed to cause ADE upon primary DENV infection [9]. Antibodies produced against prM protein and the fusion loop in E protein have been shown to play a role in ADE [4]. In addition, FcγR-mediated DENV infection was found to suppress effectively the host antiviral innate immunity, thereby further promoting DENV intracellular replication [10]. Furthermore, enhanced disease severity upon secondary heterologous DENV infection has also been attributed to the reactivation of weakly cross-reactive memory T cells generated during the primary DENV infection. These T cells display limited antiviral capacity but secrete high amounts of pro-inflammatory cytokines such as TNF-α that contribute to plasma leakage [11]. This concept known as ‘original antigenic sin’ remains however controversial with conflicting studies and lack of strong evidence in dengue patients.
Prevalence, risk factors and impact of occult HCV infection on liver morbidity among haemodialysis patients: hospital-based cross-sectional study
Published in Scandinavian Journal of Gastroenterology, 2020
Abdulrahman Alduraywish, Mostafa Ragheb, Ibrahim Taher, Nageh Louis, Khaled Aldossari, Rania Kishk
Infection with the hepatitis C virus (HCV) is a worldwide health problem that affects 2.5% of the population [1]. The virus belongs to the family of Flaviviridae and genus Hepacivirus [2]. Diagnosis of HCV infection is made by assessment of risk factors, clinical manifestations, abnormal liver enzymes and anti-HCV (HCV Ab) seroreactivity [3]. This common asymptomatic infection mostly turns chronic and diagnosis is made accidentally during routine testing. Although acute hepatitis is uncommonly encountered, HCV infection is related to variable liver morbidities that range from chronic hepatitis, cirrhosis and hepatocellular carcinoma [4,5]. Treatment of HCV depends largely on the presence of HCV RNA viraemia and more recently the direct-acting antiviral (DAA) that eliminated the virus in more than 90% of naïve cases [6,7].
Post-exposure prophylactic vaccine candidates for the treatment of human Risk Group 4 pathogen infections
Published in Expert Review of Vaccines, 2020
James Logue, Ian Crozier, Peter B Jahrling, Jens H Kuhn
Finally, tick-borne encephalitis virus (TBEV; Flaviviridae: Flavivirus) is generally transmitted by ixodid ticks in Western (Ixodes ricinus) and Eastern (Ixodes persulcatus) Europe. The virus is maintained by over 100 species of wild animals, including voles, deer, and domestic animals such as sheep [122–124]. Although patients infected with TBEV normally only present with an initial, nonspecific febrile phase, 20–30% of patients progress to a second stage of disease with CNS signs (meningitis, encephalitis, or both). Lethality is generally 1–2%, but 30–60% of patients develop chronic neuropsychiatric sequelae [125,126]. Three different vaccines for pre-exposure disease prevention (IPVE, FSME-IMMUN, and Encepur) are generally available in endemic regions [127]. However, fears over the potential of antibody-dependent disease enhancement or increased viral infectivity caused by ‘sub-optimal’ concentrations of virus-specific antibodies have hampered further vaccine development [128]. For this reason and the potential of other adverse effects [129], none of these vaccines are licensed by the US FDA. Vaccine use is neither recommended by the US Centers for Disease Control and Prevention (CDC) nor the WHO except for high-risk individuals, such as laboratory workers or workers with high exposure to potentially infected host ticks [130,131]. Multiple studies into the use of antibody treatments as PEP have produced promising results in laboratory mice with no disease enhancement [132,133].
Related Knowledge Centers
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