Phylogenetic analysis of the promoter element 2 of paramyxo- and filoviruses.

Paramyxo- and filovirus genomes are equipped with bipartite promoters at their 3' ends to initiate RNA synthesis. The two elements, the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2), are separated by a spacer region that must be precisely a multiple of 6 nucleotides (nts), indicating these viruses adhere to the "rule of six." However, our knowledge of PE2 has been limited to a narrow spectrum of virus species. In this study, a comparative analysis of 1,647 paramyxoviral genomes from a public database revealed that the paramyxovirus PE2 can be clearly categorized into two distinct subcategories: one marked by C repeats at every six bases (exclusive to the subfamily Orthoparamyxovirinae) and another characterized by CG repeats every 6 nts (observed in the subfamilies Avulavirinae and Rubulavirinae). This unique pattern collectively mirrors the evolutionary lineage of these subfamilies. Furthermore, we showed that PE2 of the Rubulavirinae, with the exception of mumps virus, serves as part of the gene-coding region. This may be due to the fact that the Rubulavirinae are the only paramyxoviruses that cannot propagate without RNA editing. Filoviruses have three to eight consecutive uracil repeats every six bases (UN5) in PE2, which is located in the 3' end region of the genome. We obtained PE2 sequences from 2,195 filoviruses in a public database and analyzed the sequence conservation among virus species. Our results indicate that the continuity of UN5 hexamers is consistently maintained with a high degree of conservation across virus species. IMPORTANCE: The genomic intricacies of paramyxo- and filoviruses are highlighted by the bipartite promoters-promoter element 1 (PE1) and promoter element 2 (PE2)-at their 3' termini. The spacer region between these elements follows the "rule of six," crucial for genome replication. By a comprehensive analysis of paramyxoviral genome sequences, we identified distinct subcategories of PE2 based on C and CG repeats that were specific to Orthoparamyxovirinae and Avulavirinae/Rubulavirinae, respectively, mirroring their evolutionary lineages. Notably, the PE2 of Rubulavirinae is integrated into the gene-coding region, a unique trait potentially linked to its strict dependence on RNA editing for virus growth. This study also focused on the PE2 sequences in filovirus genomes. The strict conservation of the continuity of UN5 among virus species emphasizes its crucial role in viral genome replication.

Prevention of respiratory virus transmission by resident memory CD8+ T cells.

An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd immunity. Although this strategy has proved successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies1. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to respond rapidly to respiratory virus infections2-6. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to the extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8+ T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8+ T cells requires the antiviral cytokine interferon-γ (IFNγ) and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8+ T cells in the respiratory tract can have important roles in protecting the host against viral disease and limiting viral spread throughout the population.

Reverse Genetics Systems for the De Novo Rescue of Diverse Members of Paramyxoviridae.

Paramyxoviruses place significant burdens on both human and wildlife health; while some paramyxoviruses are established within human populations, others circulate within diverse animal reservoirs. Concerningly, bat-borne paramyxoviruses have spilled over into humans with increasing frequency in recent years, resulting in severe disease. The risk of future zoonotic outbreaks, as well as the persistence of paramyxoviruses that currently circulate within humans, highlights the need for efficient tools through which to interrogate paramyxovirus biology. Reverse genetics systems provide scientists with the ability to rescue paramyxoviruses de novo, offering versatile tools for implementation in both research and public health settings. Reverse genetics systems have greatly improved over the past 30 years, with several key innovations optimizing the success of paramyxovirus rescue. Here, we describe the significance of such advances and provide a generally applicable guide for the development and use of reverse genetics systems for the rescue of diverse members of Paramyxoviridae.

Global genetic diversity of measles virus (Paramyxoviridae: Morbillivirus: Morbillivirus hominis): historical aspects and current state.

Monitoring the circulation of the measles virus and studying its genetic diversity is an important component of the measles elimination program. A methodological approach to molecular genetic studies and their interpretation in the measles surveillance was developed in the early 2000s. During its development, clear areas of circulation of each genotype of the virus were identified, therefore, the determination of viruses' genotypes was proposed to monitor circulation and identify transmission pathways. However, in the future, due to a significant decrease in the number of active genotypes, an approach based on sub-genotyping was proposed: determining not only the genotype of the virus, but also its genetic lineage/genetic variant. The Global Measles and Rubella Laboratory Network (GMRLN) systematically monitors the circulation of the measles virus at the sub-genotypic level, depositing the results in a specialized database MeaNS2. It is this database that is the most complete and reliable source of information about the genetic characteristic of measles viruses. This review presents both historical information and the latest data on the global genetic diversity of the measles virus.

Regulation of host gene expression by J paramyxovirus.

Paramyxoviruses are negative-sense, single-stranded RNA viruses that are associated with numerous diseases in humans and animals. J paramyxovirus (JPV) was first isolated from moribund mice (Mus musculus) with hemorrhagic lung lesions in Australia in 1972. In 2016, JPV was classified into the newly established genus Jeilongvirus. Novel jeilongviruses are being discovered worldwide in wildlife populations. However, the effects of jeilongvirus infection on host gene expression remains uncharacterized. To address this, cellular RNA from JPV-infected mouse fibroblasts was collected at 2, 4, 8, 12, 16, 24, and 48 hours post-infection (hpi) and were sequenced using single-end 75 base pairs (SE75) sequencing chemistry on an Illumina NextSeq platform. Differentially expressed genes (DEGs) between the virus-infected replicates and mock replicates at each timepoint were identified using the Tophat2-Cufflinks-Cuffdiff protocol. At 2 hpi, 11 DEGs were identified in JPV-infected cells, while 1,837 DEGs were detected at 48 hpi. A GO analysis determined that the genes at the earlier timepoints were involved in interferon responses, while there was a shift towards genes that are involved in antigen processing and presentation processes at the later timepoints. At 48 hpi, a KEGG analysis revealed that many of the DEGs detected were involved in pathways that are important for immune responses. qRT-PCR verified that Rtp4, Ifit3, Mx2, and Stat2 were all upregulated during JPV infection, while G0s2 was downregulated. After JPV infection, the expression of inflammatory and antiviral factors in mouse fibroblasts changes significantly. This study provides crucial insight into the different arms of host immunity that mediate Jeilongvirus infection. Understanding the pathogenic mechanisms of Jeilongvirus will lead to better strategies for the prevention and control of potential diseases that may arise from this group of viruses.

Paramyxoviruses: Pathogenesis, Vaccines, Antivirals, and Prototypes for Pandemic Preparedness.

The Paramyxoviridae family includes established human pathogens such as measles virus, mumps virus, and the human parainfluenza viruses; highly lethal zoonotic pathogens such as Nipah virus; and a number of recently identified agents, such as Sosuga virus, which remain poorly understood. The high human-to-human transmission rate of paramyxoviruses such as measles virus, high case fatality rate associated with other family members such as Nipah virus, and the existence of poorly characterized zoonotic pathogens raise concern that known and unknown paramyxoviruses have significant pandemic potential. In this review, the general life cycle, taxonomic relationships, and viral pathogenesis are described for paramyxoviruses that cause both systemic and respiratory system-restricted infections. Next, key gaps in critical areas are presented, following detailed conversations with subject matter experts and based on the current literature. Finally, we present an assessment of potential prototype pathogen candidates that could be used as models to study this important virus family, including assessment of the strengths and weaknesses of each potential prototype.

Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein.

IMPORTANCE: Genetically diverse paramyxoviruses are united in their presentation of a receptor-binding protein (RBP), which works in concert with the fusion protein to facilitate host-cell entry. The C-terminal head region of the paramyxoviral RBP, a primary determinant of host-cell tropism and inter-species transmission potential, forms structurally distinct classes dependent upon protein and glycan receptor specificity. Here, we reveal the architecture of the C-terminal head region of the RBPs from Nariva virus (NarV) and Mossman virus (MosV), two archetypal rodent-borne paramyxoviruses within the recently established genus Narmovirus, family Paramyxoviridae. Our analysis reveals that while narmoviruses retain the general architectural features associated with paramyxoviral RBPs, namely, a six-bladed ß-propeller fold, they lack the structural motifs associated with known receptor-mediated host-cell entry pathways. This investigation indicates that the RBPs of narmoviruses exhibit pathobiological features that are distinct from those of other paramyxoviruses.

RNA sequencing of avian paramyxovirus (Paramyxoviridae, Avulavirinae) isolates from wild mallards in Belgium, 2021: complete genomes and coinfections.

We used untargeted RNA sequencing to characterize three Avulavirinae isolates from pooled samples obtained from wild mallards in Belgium in 2021. The complete genome sequences of two avian Orthoavulavirus-1 (AOAV-1) strains and one avian Paraavulavirus-4 (APMV-4) strain were determined confirming hemagglutination inhibition testing of the virus isolates. In addition, the applied sequencing strategy identified an avian influenza virus (AIV) coinfection in all three virus isolates, confirming weak-positive AIV realtime RT-PCR results from the original sample material. In one AOAV-1 isolate, partial sequences covering all genome segments of an AIV of subtype H11N9 could be de novo assembled from the sequencing data. Besides an AIV coinfection, RNA metagenomic data from the APMV-4 isolate also showed evidence of Alpharetrovirus and Megrivirus coinfection. In total, two AOAV-1 of Class II, genotype I.2 and one APMV-4 complete genome sequences were assembled and compared to publicly available sequences, highlighting the importance of surveillance for poultry pathogens in wild birds. Beyond the insights from full genome characterization of virus isolates, untargeted RNA sequencing strategies provide additional insights in the RNA virome of clinical samples as well as their derived virus isolates that are particularly useful when targeting wild avifauna reservoirs of poultry pathogens.

[Intranasal vaccine against COVID-19 based on a recombinant variant of the Sendai virus (Paramyxoviridae: Respirovirus) strain Moscow].

INTRODUCTION: Intranasal vaccination using live vector vaccines based on non-pathogenic or slightly pathogenic viruses is the one of the most convenient, safe and effective ways to prevent respiratory infections, including COVID-19. Sendai virus is the best suited for this purpose, since it is respiratory virus and is capable of limited replication in human bronchial epithelial cells without causing disease. The aim of the work is to design and study the vaccine properties of recombinant Sendai virus, Moscow strain, expressing secreted receptor-binding domain of SARS-CoV-2 Delta strain S protein (RBDdelta) during a single intranasal immunization. MATERIALS AND METHODS: Recombinant Sendai virus carrying insertion of RBDdelta transgene between P and M genes was constructed using reverse genetics and synthetic biology methods. Expression of RBDdelta was analyzed by Western blot. Vaccine properties were studied in two models: Syrian hamsters and BALB/c mice. Immunogenicity was evaluated by ELISA and virus-neutralization assays. Protectiveness was assessed by quantitation of SARS-CoV-2 RNA in RT-PCR and histological analysis of the lungs. RESULTS: Based on Sendai virus Moscow strain, a recombinant Sen-RBDdelta(M) was constructed that expressed a secreted RBDdelta immunologically identical to natural SARS-CoV-2 protein. A single intranasal administration of Sen-RBDdelta(M) to hamsters and mice significantly, by 15 and 107 times, respectively, reduced replicative activity of SARS-CoV-2 in lungs of animals, preventing the development of pneumonia. An effective induction of virus-neutralizing antibodies has also been demonstrated in mice. CONCLUSION: Sen-RBDdelta(M) is a promising vaccine construct against SARS-CoV-2 infection and has a protective properties even after a single intranasal introduction.

[Selection of conditions for effective inactivation of Pseudopestis avium virus (Paramyxoviridae: Orthoavulovirus: Avian orthoavulovirus 1) for the production of a Newcastle disease vaccine].

INTRODUCTION: Newcastle disease (ND) is classified as especially dangerous pathogen. Its primary source is an infected or recovered bird. The virus shedding begins just in a day after infection, and virus remains in the body for another 2-4 months after the recovery. The complexity of the final elimination of the causative agent of the disease lies in its ability for long-term preservation in the external environment and the possibility of constant circulation in one complex between groups of birds of different sex and age. Therefore, the main element of protecting birds from ND is immunoprophylaxis that is based on vaccines containing an inactivated ND virus (NDV). The aim of the work ‒ is to optimize the parameters of inactivation of the NDV actual strain H with formaldehyde at final concentrations of 0.01, 0.025, 0.05, and 0.1% under temperature conditions of 20 2 and 37 0.5 C. MATERIALS AND METHODS: We used a virus-containing suspension of the NDV strain H with an initial biological activity of 10.75 lg EID50/cm3 grown by cultivation in 10-day-old developing chick embryos. RESULTS: On the 16th day after the administration of the tested suspensions of NDV inactivated at different temperatures and concentrations of the inactivant , the geometric mean titers of antibodies to NDV in sera of vaccinated birds were at least 1 : 63 in the hemagglutination inhibition reaction, indicating that the studied inactivated suspensions were antigenically active. CONCLUSION: The optimal parameters of the inactivation mode (final concentration, temperature and time of inactivation) of the NDV strain H were established. The inactivation process at 37 0.5 C with inactivant concentrations of 0.01, 0.025, 0.05, and 0.1% lasts up to 72, 22, 18, and 12 hours, respectively. The inactivation process at 20 2 C with inactivant concentrations of 0.05 and 0.1% lasts up to 22 and 18 hours, respectively.

Genomic Characterization of a Relative of Mumps Virus in Lesser Dawn Bats of Southeast Asia.

The importance of genomic surveillance on emerging diseases continues to be highlighted with the ongoing SARS-CoV-2 pandemic. Here, we present an analysis of a new bat-borne mumps virus (MuV) in a captive colony of lesser dawn bats (Eonycteris spelaea). This report describes an investigation of MuV-specific data originally collected as part of a longitudinal virome study of apparently healthy, captive lesser dawn bats in Southeast Asia (BioProject ID PRJNA561193) which was the first report of a MuV-like virus, named dawn bat paramyxovirus (DbPV), in bats outside of Africa. More in-depth analysis of these original RNA sequences in the current report reveals that the new DbPV genome shares only 86% amino acid identity with the RNA-dependent RNA polymerase of its closest relative, the African bat-borne mumps virus (AbMuV). While there is no obvious immediate cause for concern, it is important to continue investigating and monitoring bat-borne MuVs to determine the risk of human infection.

[Mumps virus (Paramyxoviridae: Orthorubulavirus: Mumps orthorubulavirus) genotyping as a component of laboratory confirmation of infection].

INTRODUCTION: Mumps is a viral infection of high social significance. National program Elimination of measles and rubella and achievement of a stable sporadic incidence of epidemic mumps in the Russian Federation (20212025) sets the aim of gradual integration of mumps surveillance into the existing measles and rubella surveillance system. One of the key components of surveillance system is a laboratory confirmation of mumps cases. There are two approaches for laboratory confirmation of mumps cases, based on serological or molecular genetic methods. The aim of the work is molecular genetic characteristic of the mumps viruses (MuVs) circulated in the Russian Federation in 2022. MATERIALS AND METHODS: Samples of swabs from the inner surface of the cheek of 11 patients with mumps were collected for the study. Viral RNA was isolated directly from the samples. The isolated RNA was used as a matrix for RT-PCR. PCR products were sequenced using the Sanger method, and phylogenetic analysis was performed using the MEGA-X software. RESULTS: The MuV genotype G was detected in all samples. Phylogenetic analysis showed the presence of two virus genetic groups G-1 and G-2 that were significantly different from the viruses circulating in other countries. CONCLUSION: The identification of two MuV genetic groups in a limited area suggests a high genetic diversity of the pathogen.

Structure of the Newcastle Disease Virus L protein in complex with tetrameric phosphoprotein.

Newcastle disease virus (NDV) belongs to Paramyxoviridae, which contains lethal human and animal pathogens. NDV RNA genome is replicated and transcribed by a multifunctional 250 kDa RNA-dependent RNA polymerase (L protein). To date, high-resolution structure of NDV L protein complexed with P protein remains to be elucidated, limiting our understanding of the molecular mechanisms of Paramyxoviridae replication/transcription. Here, we used cryo-EM and enzymatic assays to investigate the structure-function relationship of L-P complex. We found that C-terminal of CD-MTase-CTD module of the atomic-resolution L-P complex conformationally rearranges, and the priming/intrusion loops are likely in RNA elongation conformations different from previous structures. The P protein adopts a unique tetrameric organization and interacts with L protein. Our findings indicate that NDV L-P complex represents elongation state distinct from previous structures. Our work greatly advances the understanding of Paramyxoviridae RNA synthesis, revealing how initiation/elongation alternates, providing clues for identifying therapeutic targets against Paramyxoviridae.

Potently neutralizing human mAbs against the zoonotic pararubulavirus Sosuga virus.

Sosuga virus (SOSV) is a recently discovered paramyxovirus with a single known human case of disease. There has been little laboratory research on SOSV pathogenesis or immunity, and no approved therapeutics or vaccines are available. Here, we report the discovery of human mAbs from the circulating memory B cells of the only known human case and survivor of SOSV infection. We isolated 6 mAbs recognizing the functional attachment protein hemagglutinin-neuraminidase (HN) and 18 mAbs against the fusion (F) protein. The anti-HN mAbs all targeted the globular head of the HN protein and could be organized into 4 competition-binding groups that exhibited epitope diversity. The anti-F mAbs can be divided into pre- or postfusion conformation-specific categories and further into 8 competition-binding groups. The only Ab in the panel that did not display neutralization activity was the single postfusion-specific anti-F mAb. Most of the anti-HN mAbs were more potently neutralizing than the anti-F mAbs, with mAbs in 1 of the HN competition-binding groups possessing ultrapotent (<1 ng/mL) half-maximal inhibitory virus neutralization values. These findings provide insight into the molecular basis for human Ab recognition of paramyxovirus surface proteins and the mechanisms of SOSV neutralization.

Discovery and characterization of novel paramyxoviruses from bat samples in China.

Many paramyxoviruses are responsible for a variety of mild to severe human and animal diseases. Based on the novel discoveries over the past several decades, the family Paramyxoviridae infecting various hosts across the world includes 4 subfamilies, 17 classified genera and 78 species now. However, no systematic surveys of bat paramyxoviruses are available from the Chinese mainland. In this study, 13,064 samples from 54 bat species were collected and a comprehensive paramyxovirus survey was conducted. We obtained 94 new genome sequences distributed across paramyxoviruses from 22 bat species in seven provinces. Bayesian phylodynamic and phylogenetic analyses showed that there were four different lineages in the Jeilongvirus genus. Based on available data, results of host and region switches showed that the bat colony was partial to interior, whereas the rodent colony was exported, and the felines and hedgehogs were most likely the intermediate hosts from Scotophilus spp. rather than rodents. Based on the evolutionary trend, genus Jeilongvirus may have originated from Mus spp. in Australia, then transmitted to bats and rodents in Africa, Asia and Europe, and finally to bats and rodents in America.

Tissue replication and mucosal swab detection of Sosuga virus in Syrian hamsters in the absence of overt tissue pathology and clinical disease.

Human infection with Sosuga virus (SOSV), a recently discovered pathogenic paramyxovirus, has been reported in one individual to date. No animal models of disease are currently available for SOSV. Here, we describe initial characterization of experimental infection in Syrian hamsters, including kinetics of virus dissemination and replication, and the corresponding clinical parameters, immunological responses, and histopathology. We demonstrate susceptibility of hamsters to infection in the absence of clinical signs or significant histopathologic findings in tissues.

Thermostability and Immunogenicity of Genotype II Avian Orthoavulavirus (AOaV-1) Isolates from Duck (Anas platyrhynchos) and Parrot (Eclectusroratus).

Newcastle disease (ND) is a highly contagious viral disease of poultry causing significant economic losses worldwide. Vaccination is considered the most reliable approach to curb the economic menace that is ND, but the thermolabile nature of Newcastle disease virus (NDV) vaccination poses a significant threat to its protective efficacy. This study aimed to profile the thermostability of NDV isolates from duck (As/Km/19/44) and parrot (As/WB/19/91) and evaluate their immunogenic potential in chicks. Fusion protein cleavage site (FPCS) and phylogenetic analysis demonstrated the lentogenic nature of both the isolates/strains and classified them as class II genotype II NDV. The characterized NDV isolates were adapted in specific-pathogen-free (SPF) chicks by serially passaging. Biological pathogenicity assessment of chicken-adapted As/Km/19/44 (PSD44C) and As/WB/19/91 (PSP91C) revealed both the isolates to be avirulent with a mean death time (MDT) of more than 90 h and an intracerebral pathogenicity index (ICPI) ranging from 0.2 to 0.4. Both of the NDV isolates displayed varied thermostability profiles. PSD44C was the most thermostable strain as compared to PSP91C and the commercially available LaSota vaccine strain. The immunogenicity of PSD44C and LaSota was significantly higher than PSP91C. Based on these results, it is concluded that NDV isolate PSD44C is more thermostable and immunogenic when administered intraocularly without any adverse effects. Therefore, PSD44C is suitable for further research and vaccine development.

Human metapneumovirus M2-2 protein inhibits RIG-I signaling by preventing TRIM25-mediated RIG-I ubiquitination.

Retinoic acid-inducible gene I (RIG-I) is a receptor that senses viral RNA and interacts with mitochondrial antiviral signaling (MAVS) protein, leading to the production of type I interferons and inflammatory cytokines to establish an antiviral state. This signaling axis is initiated by the K63-linked RIG-I ubiquitination, mediated by E3 ubiquitin ligases such as TRIM25. However, many viruses, including several members of the family Paramyxoviridae and human respiratory syncytial virus (HRSV), a member of the family Pneumoviridae, escape the immune system by targeting RIG-I/TRIM25 signaling. In this study, we screened human metapneumovirus (HMPV) open reading frames (ORFs) for their ability to block RIG-I signaling reconstituted in HEK293T cells by transfection with TRIM25 and RIG-I CARD (an N-terminal CARD domain that is constitutively active in RIG-I signaling). HMPV M2-2 was the most potent inhibitor of RIG-I/TRIM25-mediated interferon (IFN)-ß activation. M2-2 silencing induced the activation of transcription factors (IRF and NF-kB) downstream of RIG-I signaling in A549 cells. Moreover, M2-2 inhibited RIG-I ubiquitination and CARD-dependent interactions with MAVS. Immunoprecipitation revealed that M2-2 forms a stable complex with RIG-I CARD/TRIM25 via direct interaction with the SPRY domain of TRIM25. Similarly, HRSV NS1 also formed a stable complex with RIG-I CARD/TRIM25 and inhibited RIG-I ubiquitination. Notably, the inhibitory actions of HMPV M2-2 and HRSV NS1 are similar to those of V proteins of several members of the Paramyxoviridae family. In this study, we have identified a novel mechanism of immune escape by HMPV, similar to that of Pneumoviridae and Paramyxoviridae family members.

Classification of new morbillivirus and jeilongvirus sequences from bats sampled in Brazil and Malaysia.

As part of a broad One Health surveillance effort to detect novel viruses in wildlife and people, we report several paramyxovirus sequences sampled primarily from bats during 2013 and 2014 in Brazil and Malaysia, including seven from which we recovered full-length genomes. Of these, six represent the first full-length paramyxovirid genomes sequenced from the Americas, including two that are the first full-length bat morbillivirus genome sequences published to date. Our findings add to the vast number of viral sequences in public repositories, which have been increasing considerably in recent years due to the rising accessibility of metagenomics. Taxonomic classification of these sequences in the absence of phenotypic data has been a significant challenge, particularly in the subfamily Orthoparamyxovirinae, where the rate of discovery of novel sequences has been substantial. Using pairwise amino acid sequence classification (PAASC), we propose that five of these sequences belong to members of the genus Jeilongvirus and two belong to members of the genus Morbillivirus. We also highlight inconsistencies in the classification of Tupaia virus and Mòjiang virus using the same demarcation criteria and suggest reclassification of these viruses into new genera. Importantly, this study underscores the critical importance of sequence length in PAASC analysis as well as the importance of biological characteristics such as genome organization in the taxonomic classification of viral sequences.

In Vitro Growth, Receptor Usage and Pathogenesis of Feline Morbillivirus in the Natural Host.

Feline morbillivirus (FeMV) is a recently discovered virus belonging to the genus Morbillivirus of the virus family Paramyxoviridae. Often, the virus has been detected in urine of cats with a history of urinary disease and has a worldwide distribution. Currently, it is unclear which receptor the virus uses to enter the target cells. Furthermore, many aspects of FeMV biology in vivo, including tissue tropism, pathogenesis, and virus excretion in the natural host remain unclear. In this study we analyzed the replication of FeMV in various cell lines. Secondly, we tested if the presence of feline SLAMF1 (Signaling Lymphocytic Activation Molecule family 1/CD150, principal entry receptor for other members of the Morbillivirus genus) improved FeMV replication efficiency in vitro. Finally, to elucidate in vivo biology in cats, as a natural host for FeMV, we experimentally infected a group of cats and monitored clinical symptoms, viremia, and excretion of the virus during the course of 56 days. Our study showed that FeMV shares some features with other morbilliviruses like the use of the SLAMF1 receptor. For the first time, experimental infection of SPF cats showed that FeMV does not induce an acute clinical disease like other morbilliviruses but can induce lesions in the kidneys, including tubulointerstitial nephritis. Further investigations are needed to confirm the site and dynamics of replication of FeMV in the urinary tract and the longer-term impact of FeMV-induced lesions on the renal function. Whether FeMV infection can result in chronic kidney disease will require the monitoring of cats over a longer period.