The family Pneumoviridae comprises large enveloped negative-sense RNA viruses. This taxon was formerly a subfamily within the Paramyxoviridae, but was reclassified in 2016 as a family with two genera, Orthopneumovirus and Metapneumovirus. Pneumoviruses infect a range of mammalian species, while some members of the Metapneumovirus genus may also infect birds. Some viruses are specific and pathogenic for humans, such as human respiratory syncytial virus and human metapneumovirus. There are no known vectors for pneumoviruses and transmission is thought to be primarily by aerosol droplets and contact. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Pneumoviridae, which is available at www.ictv.global/report/pneumoviridae.

The family Paramyxoviridae consists of large enveloped RNA viruses infecting mammals, birds, reptiles and fish. Many paramyxoviruses are host-specific and several, such as measles virus, mumps virus, Nipah virus, Hendra virus and several parainfluenza viruses, are pathogenic for humans. The transmission of paramyxoviruses is horizontal, mainly through airborne routes; no vectors are known. This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) Report on the family Paramyxoviridae. which is available at ictv.global/report/paramyxoviridae.

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The global increase in measles vaccination has resulted in a significant reduction of measles mortality. The standard route of administration for the live-attenuated measles virus (MV) vaccine is subcutaneous injection, although alternative needle-free routes, including aerosol delivery, are under investigation. In vitro, attenuated MV has a much wider tropism than clinical isolates, as it can use both CD46 and CD150 as cellular receptors. To compare the in vivo tropism of attenuated and pathogenic MV, we infected cynomolgus macaques with pathogenic or attenuated recombinant MV expressing enhanced green fluorescent protein (GFP) (strains IC323 and Edmonston, respectively) via the intratracheal or aerosol route. Surprisingly, viral loads and cellular tropism in the lungs were similar for the two viruses regardless of the route of administration, and CD11c-positive cells were identified as the major target population. However, only the pathogenic MV caused significant viremia, which resulted in massive virus replication in B and T lymphocytes in lymphoid tissues and viral dissemination to the skin and the submucosa of respiratory epithelia. Attenuated MV was rarely detected in lymphoid tissues, and when it was, only in isolated infected cells. Following aerosol inhalation, attenuated MV was detected at early time points in the upper respiratory tract, suggesting local virus replication. This contrasts with pathogenic MV, which invaded the upper respiratory tract only after the onset of viremia. This study shows that despite in vitro differences, attenuated and pathogenic MV show highly similar in vivo tropism in the lungs. However, systemic spread of attenuated MV is restricted.Measles virus (MV) is one of the most contagious human viruses and is transmitted via aerosols or by direct contact with contaminated respiratory secretions. Clinical symptoms appear approximately 2 weeks after infection and include fever, rash, cough, coryza, and conjunctivitis (20). Measles is associated with immunosuppression, resulting in increased susceptibility to opportunistic infections. While significant progress has been made in global control programs, 164,000 deaths were attributed to measles in 2008 (46).MV was first isolated in cell culture in 1954 (16). This Edmonston wild-type MV strain was passaged multiple times in primary human kidney and amnion cells and adapted to eggs and chicken embryo fibroblasts to produce the live-attenuated Edmonston-B vaccine virus (15), which was later replaced by the more attenuated MV strains (Edmonston-Zagreb, Moraten, and Schwarz) (34). These vaccines have been shown to be safe and effective, and high coverage in two-dose regimens has successfully interrupted endemic MV transmission in large geographic areas (6).For many years, laboratory-adapted MV-Edmonston strains were used as the prototype virus and were shown to display a wide cellular tropism in vitro. The virus efficiently infected epithelial cells, which were considered the target cells for primary MV infection in vivo (22). In 1993,...

Infectious viruses so precisely fit their hosts that the study of natural viral infection depends on host-specific mechanisms that affect viral infection. For human parainfluenza virus 3, a prevalent cause of lower respiratory tract disease in infants, circulating human viruses are genetically different from viruses grown in standard laboratory conditions; the surface glycoproteins that mediate host cell entry on circulating viruses are suited to the environment of the human lung and differ from those of viruses grown in cultured cells. Polarized human airway epithelium cultures have been used to represent the large, proximal airways of mature adult airways. Here we modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids derived from human pluripotent stem cells contain mesoderm and pulmonary endoderm and develop into branching airway and alveolar structures. Whole-genome sequencing analysis of parainfluenza viruses replicating in the organoids showed maintenance of nucleotide identity, suggesting that no selective pressure is exerted on the virus in this tissue. Infection with parainfluenza virus led to viral shedding without morphological changes, while respiratory syncytial virus infection induced detachment and shedding of infected cells into the lung organoid lumens, reminiscent of parainfluenza and respiratory syncytial virus in human infant lungs. Measles virus infection, in contrast, induced syncytium formation. These human stem cell-derived lung organoids may serve as an authentic model for respiratory viral pathogenesis in the developing or infant lung, recapitulating respiratory viral infection in the host. IMPORTANCE Respiratory viruses are among the first pathogens encountered by young children, and the significant impact of these viral infections on the developing lung is poorly understood. Circulating viruses are suited to the environment of the human lung and are different from those of viruses grown in cultured cells. We modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids, derived from human pluripotent stem cells, develop into branching airway and alveolar structures and provide a tissue environment that maintains the authentic viral genome. The lung organoids can be genetically engineered prior to differentiation, thereby generating tissues bearing or lacking specific features that may be relevant to viral infection, a feature that may have utility for the study of host-pathogen interaction for a range of lung pathogens.

Measles virus (MV) is the type species of the Morbillivirus genus and its RNA-dependent RNA polymerase complex is comprised of two viral polypeptides, the large (L) and the phospho-(P) proteins. Sequence alignments of morbillivirus L polymerases have demonstrated the existence of three well-conserved domains (D1, D2, and D3) which are linked by two variable hinges (H1 and H2). Epitope tags (c-Myc) were introduced into H1 and H2 to investigate the tolerance of the variable regions to insertions and to probe the flexibility of the proposed domain structures to spatial reorientation. Insertion into H1 abolished polymerase activity whereas introduction into H2 had no effect. The open reading frame of enhanced green fluorescent protein was also inserted into the H2 region of the MV L gene to extend these observations. This resulted in a recombinant protein that was both functional and autofluorescent, although the overall polymerase activity was reduced by over 40%. Two recombinant viruses which contained the chimeric L genes EdtagL(MMc-mycM) and EdtagL (MMEGFPM) were generated. Tagged L proteins were detectable, by indirect immunofluorescence in the case of EdtagL(MMc-mycM) and by autofluorescence in the case of EdtagL(MMEGFPM). We suggest that D3 enjoys a limited conformational independence from the other domains, indicating that the L polymerases of the Mononegavirales may function as multidomain proteins.Measles virus (MV) is the type species of the Morbillivirus genus, which is one of the seven genera of the family Paramyxoviridae. The Paramyxoviridae, Bornaviridae, Filoviridae, and Rhabdoviridae make up the order Mononegavirales, and other well-known prototypes of this grouping include Sendai, Borna disease, Ebola, and rabies viruses. The viruses are enveloped and contain single-stranded, negative-sense RNA genomes of between 9 and 19 kb. Virion RNA is complexed in a helical nucleocapsid comprised of the nucleo-(N), phospho-(P), and large (L) proteins. This ribonucleoprotein (RNP) complex is the obligatory template for viral transcription and replication and unencapsidated viral genomic RNA is transcriptionally inactive and not infectious. RNA-dependent RNA polymerase (RdRp) activity is associated with the L and P proteins (12). Genes are expressed from a single promoter at the 3Ј end of the genome. Although at present there is no direct evidence for its direct role in RNA synthesis, it is assumed that the L protein contains the polymerase activity and the P protein has an accessory role. Genetic or biochemical studies have also demonstrated other activities such as capping, methylation, and polyadenylation (1, 10, 13).It is unlikely that the L protein exists as a single globular structure because of its size, 2,183 amino acids (ϳ250 kDa) for MV. Sequence alignments of the morbillivirus L proteins revealed two highly variable regions, which we termed hinges. The first (H1) extends from residues 607 to 650 and the second (H2) is comprised of residues 1695 to 1717; the hinges may form domain boundaries (17). Alig...