The Viruses
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Viruses are classified into a variety of families based on morphologic, structural, and genetic characteristics, including the size, structure, and type of their nucleic acid (Table 16.1). The names of virus families end in the suffix viridae, for example paramyxoviridae. Viruses are classified further by the organization and function of their genetic coding and regulatory sequences, and also by the functions of specifically encoded enzymes and protein antigens. These subdivisions are called genera and end in the suffix virus such as the morbillivirus genus of the paramyxoviridae. Viruses in genera are often further divided into viral species based on differences in their genomic sequences. For example, canine distemper virus is a member of the morbillivirus genus in the family paramyxoviridae. Some human and animal viruses classified by family are listed in Table 16.1.
Measles Virus
Sunit K. Singh in Human Respiratory Viral Infections, 2014
As an alternative, measles pathogenesis has also been studied by performing infections of animal morbilliviruses in their natural hosts, mostly canine distemper virus (CDV) in ferrets. This has provided important insights into morbillivirus pathogenesis. Using a ferret-adapted rCDV strain expressing EGFP, von Messling et al. have illuminated the tropism of CDV and found many similarities to MV.86 CDV initially replicated in T- and B-lymphocytes in lymphoid organs and CDV-infected ferrets developed rash, high fever, and viremia. An initial, exclusively lymphoid phase was followed by widespread epithelial cell infection. Furthermore, the ferrets were severely immune suppressed and usually died within 2–3 weeks post inoculation, although this strongly depended on the virus strain used.86–89 In addition, a hallmark of CDV infection of both ferrets and dogs is the frequent spread of the virus into the CNS. This also directly demonstrates a key limitation of using an animal morbillivirus as a model for measles. MV rarely causes CNS complications in humans and is normally not lethal, and therefore dramatically differs from CDV infection of ferrets.
Human Paramyxoviruses and Infections of the Central Nervous System
Sunit K. Singh, Daniel Růžek in Neuroviral Infections, 2013
As the prototypic morbillivirus, and probably the most well-known paramyxovirus, more is understood about the molecular and cell biology of MV than any of the other viruses we will discuss. Following the eradication of smallpox, MV is probably the most transmissible human virus having an R0 between 12 and 18 (Moss and Griffin 2006). The virus causes a systemic disease primarily of the immune system and is associated with high levels of morbidity and mortality in the developing world, largely as a consequence of the profound immune suppression induced in infected individuals (Avota et al. 2010). The first written account of MV infection dates from the 9th century and is ascribed to the Arabian physician Abu Becr, also known as Rhazes of Baghdad, who dated the first description of measles to the 6th century (Hirsch 1883). Phylogenetic analysis indicates that MV probably evolved from the ancestor of the closely related rinderpest virus (RPV) which predominately infects cattle (Furuse et al. 2010). However, the strict tropism displayed by current circulating wild-type MV strains for humans and some species of monkey is indicative of the typical evolution of a virus following zoonotic infection whereby the virus becomes ever more adapted to the new host. It is assumed that MV only became permanently established in human populations after the development of cities in India and the Middle East of sufficient size to fulfill the requirement of 250,000 to 500,000 people necessary to maintain endemic MV transmission (Keeling and Grenfell 1997). Consequently MV has been termed a disease of civilization due to the requirement for a sufficiently large population of naive susceptible hosts to maintain an endemic infection.
Measles-vectored vaccine approaches against viral infections: a focus on Chikungunya
Published in Expert Review of Vaccines, 2019
Christiane Gerke, Phanramphoei N. Frantz, Katrin Ramsauer, Frédéric Tangy
The genetic characteristics of the measles virus build the basis for its use as highly versatile vector. Measles virus (MV) is a member of the genus Morbillivirus in the family of Paramyxoviridae characterized by pleomorphic viral particles with sizes ranging from 150 to 350 nm. It is an enveloped virus with a non-segmented, negative-sense, single-stranded RNA genome of approximately 16 kb in length encoding six structural proteins: nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin (H), polymerase (L), and two non-structural proteins: V and C (Figure 1). Proteins H, F, and M constitute the envelope of the virus and are responsible for virus attachment, membrane fusion, and viral entry. Proteins V and C are essential in regulating viral replication and the host innate immune response. The RNA is encapsidated by protein N, whereby each protein molecule is associated with six nucleotides. This structure, together with the proteins P and L, forms a helicoidal ribonucleoprotein (RNP) complex, which serves as a template for RNA synthesis. Due to the flexibility of the helicoidal structure, the genome can tolerate large insertions of foreign genetic material [26] of up to 6 kb as long and maybe more. The only requirement is, that based on the association of each N protein with six nucleotides the genome length has to respect so-called ‘rule of six’, which means that the total number of genome nucleotides is dividable by six [27], to allow efficient replication.
In vivo nose-to-brain delivery of the hydrophilic antiviral ribavirin by microparticle agglomerates
Published in Drug Delivery, 2018
Alessandro Giuliani, Anna Giulia Balducci, Elisa Zironi, Gaia Colombo, Fabrizio Bortolotti, Luca Lorenzini, Viola Galligioni, Giampiero Pagliuca, Alessandra Scagliarini, Laura Calzà, Fabio Sonvico
The nasal route has been extensively studied for the administration of drugs directly to the CNS (Landis et al., 2012). In fact, this route exploits the olfactory region and the trigeminal nerve pathway to enable drugs’ entry into the CNS bypassing the BBB (Hanson & Frey, 2008). This delivery approach was explored for the administration of ribavirin (RBV), in view of an innovative treatment of the encephalitis associated with canine distemper virus, a major veterinary infection that could serve as a proof of concept of the approach. This virus belongs to the Morbillivirus genus as the measles virus and primarily infects dogs (Elia et al., 2008; Dal Pozzo et al., 2010). RBV is a synthetic guanosine antiviral analog. It has a broad-spectrum antiviral activity, being clinically effective against several viruses and successfully tested in vitro against several RNA and DNA virus infections (Beaucourt & Vignuzzi, 2014). The drug is currently marketed in oral dosage forms; however, it has been clinically administered as pulmonary aerosol in the treatment of respiratory syncytial virus (Li et al., 2012) and for the therapy of measles pneumonia (Safdar et al., 2009) as well as intravenously and intraventricularly for subacute sclerosing panencephalitis (Tomoda et al., 2003; Garg, 2008). However, the latter two approaches are plagued by adverse effects and exploit a highly invasive, risky, and infection-prone administration route, remarkably fostering the development of an alternative delivery route such as nasal administration. Our group showed that measurable brain concentrations of RBV can be obtained in rats after intranasal administration of a RBV aqueous solution. In particular, it was evidenced that 20 min after nasal administration, RBV was highly concentrated in the olfactory bulb and in other brain structures after nasal administration (Colombo et al., 2011).
A Review of Human Ocular RNA Virus Infections Excluding Coronavirus, Human T-Cell Lymphotropic Virus, and Arboviruses
Published in Ocular Immunology and Inflammation, 2023
Derrick P. Smit, Dony K. Mathew, Moncef Khairallah, Steven Yeh, Emmett T. Cunningham
Measles is a highly contagious viral disease affecting mostly children and young adults. This disease is caused by morbillivirus, a member of the Paramyxoviridae family of enveloped, non-segmented, negative-sense RNA viruses.14
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