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Order Bunyavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
According to the latest ICTV issues (Hughes et al. 2020), the Peribunyaviridae family contains 4 genera and 112 species. Typical for the family are members of the Orthobunyavirus genus, first, Bunyamwera virus (BUNV). Most orthobunyaviruses are transmitted by mosquitoes, and human infections occur through blood feeding by a vector arthropod. The orthobunyaviruses are associated with a broad spectrum of human disease, including encephalitides (La Crosse virus or LACV), febrile illnesses (BUNV), and viral haemorrhagic fever (Ngari virus, NRIV, Garissa variant). The adverse veterinary outcomes include fetal abnormalities and abortion storms among livestock (Cache Valley virus, CVV, and Schmallenberg virus, SBV; Hughes et al. 2020).
Bunyaviruses
Published in Sunit K. Singh, Daniel Růžek, Neuroviral Infections, 2013
Patrik Kilian, Vlasta Danielová, Daniel Růžek
During the extraneural phase of the infection, the virus primarily replicates in striated muscles and to a lesser extent in smooth or heart muscles. The virus is then thought to penetrate the lymphatic system and access the blood, then viremia appears. During the viremic phase, the virus crosses the blood—brain barrier and invades the CNS. Replication in the CNS is highly age-dependent. In suckling mice, there is a pancellular infection, whereas in adult mice the virus primarily replicates in neurons (Griot et al. 1993). The LACV also induces apoptosis of the neurons (Pekosz et al. 1996). Death occurs approximately 3-4 days after infection. However, most of the infections do not progress to the CNS phase. The basic steps taken by California encephalitis viruses are depicted in Figure 4.4. An alternative model of orthobunyavirus pathogenesis has been published by Bennett et al. (2008). In this case, i.e. an intraperitoneal infection of a weanling Swiss Webster mouse with the LACV, the virus initially replicated in tissues near the site of inoculation and then unidentified cells in nasal turbinates became infected via the blood stream. In this case, olfactory neurons facilitated virus entry into the CNS. Together with the previous observation, it seems that the virus can use more than one method for entry into the CNS. The observed differences in the course of the infection may be due to the use of different strains of mice or virus used in each study or due to different sites of inoculation.
Signal peptide peptidase: a potential therapeutic target for parasitic and viral infections
Published in Expert Opinion on Therapeutic Targets, 2022
Christopher Schwake, Michael Hyon, Athar H. Chishti
Several other notable human viruses utilize host SPP during their infective cycle. (Z-LL)2 ketone inhibition resulted in Ebola virus glycoprotein particle entry blockage through cathepsin B/L-mediated entry [82]. (Z-LL)2 ketone was shown to directly inhibit recombinant cathepsin B and L that utilize cysteine residue mediated catalysis [82], a finding consistent with the fact that (Z-LL)2 ketone was first developed as a cysteine protease [20]. A closely related filovirus, Lake Victoria Marburgvirus Musoke (MARV), was not inhibited effectively with (Z-LL)2 ketone presumably due to its CatB/CatL-independent cell entry [83]. (Z-LL)2 ketone was also effective at inhibiting cell entry of pseudotyped particles containing MERS-CoV and SARS-CoV glycoproteins through inhibition of cathepsin L [82], which is required for SARS and MERS entry [84]. Fewer studies have examined the role of SPP in other viral infections. The Bunyamwera Orthobunyavirus glycoprotein is processed by both signal peptidase and signal peptide peptidase [85]. This observation served as an important example of viral protein precursor cleavage in the genus Orthobunyavirus, which could lead to the development of targeted interventions of SPP-mediated processing in future studies. In classical swine fever virus (CSFV), SPP was found to play a crucial role in increasing capsid protein quantity [86]. During infection, the 26S proteasome degraded viral capsid proteins; however, further cleavage of the C-terminal residues by SPP prevented host degradation of the capsid protein by the proteasome [87]. The C-terminal processing of CSFV core protein was directly blocked through inhibition with (Z-LL)2-ketone. Incubation with (Z-LL)2-ketone resulted in a 100-fold reduction in virus viability [86]. The foamy virus envelope protein was found to act as a substrate for SPPL3 and SPPL2a/b [88]. More studies will be needed to determine the importance of host SPP processing steps during viral infection of these pathogens, thus permitting this pathway as a novel mechanistic therapeutic target for pharmacological intervention. Specifically, inhibition of viral glycoprotein processing may be an effective broad antiviral strategy in the future (Table 3).