Human Measles Virus Research Articles

Canine Distemper Virus: Origins, Mutations, Diagnosis, and Epidemiology in Mexico.

This review provides an overview of the canine distemper virus (CDV), a highly infectious pathogen causing severe disease in domestic dogs and wildlife. It shares genetic similarities with the human measles virus (HMV) in humans and the rinderpest virus (RPV) in cattle. The origin of CDV likely involves a mutation from human measles strains, possibly in the New World, with subsequent transmission to dogs. CDV has been globally observed, with an increasing incidence in various animal populations. Genomic mutations, especially in the H protein, contribute to its ability to infect different hosts. Diagnosis by molecular techniques like RT-qPCR offers rapid and sensitive detection when compared with serological tests. Genomic sequencing is vital for understanding CDV evolution and designing effective control strategies. Overall, CDV poses a significant threat, and genomic sequencing enhances our ability to manage and prevent its spread. Here, the epidemiology of CDV principally in Mexico is reviewed.

Antiviral Properties of Moringa oleifera Leaf Extracts against Respiratory Viruses.

Moringa oleifera (M. oleifera) is a plant widely used for its beneficial properties both in medical and non-medical fields. Because they produce bioactive metabolites, plants are a major resource for drug discovery. In this study, two different cultivars of leaves of M. oleifera (Salento and Barletta) were obtained by maceration or microwave-assisted extraction (MAE). We demonstrated that extracts obtained by MAE exhibited a lower cytotoxic profile compared to those obtained by maceration at concentrations ranged from 25 to 400 µg/mL, on both Vero CCL-81 and Vero/SLAM cells. We examined their antiviral properties against two viruses, i.e., the human coronavirus 229E (HCoV-229E) and measles virus (MeV), which are both responsible for respiratory infections. The extracts were able to inhibit the infection of both viruses and strongly prevented their attack and entry into the cells in a range of concentrations from 50 to 12 µg/mL. Particularly active was the variety of Salento that registered a 50% inhibitory concentration (IC50) at 21 µg/mL for HCoV-229E and at 6 µg/mL for MeV. We identified the presence of several compounds through high performance liquid chromatography (HPLC); in particular, chlorogenic and neochlorogenic acids, quercetin 3-O-β-d-glucopyranoside (QGP), and glucomoringin (GM) were mainly observed. In the end, M. oleifera can be considered a promising candidate for combating viral infections with a very strong action in the early stages of viral life cycle, probably by destructuring the viral particles blocking the virus-cell fusion.

Canine Distemper Virus Infection in the Free-Living Wild Canines, the Red Fox (Vulpes vulpes) and Jackal (Canis aureus moreoticus), in Croatia.

The canine distemper virus (CDV), a paramyxovirus that is closely related to the human measles virus and rinderpest virus of cattle, is a highly contagious viral disease in dogs and wild carnivores worldwide. CDV represents a serious threat to domestic and wild animals, especially to the conservation of endangered wild carnivores. Our study aims to investigate the occurrence of CDV in free-living wild canines in Croatia. For this purpose, 176 red foxes and 24 jackal brain samples collected in the frame of the active surveillance of rabies during winter 2021/2022 were tested. This study provided the first comprehensive overview of the prevalence and spatial distribution of CDV in the wildlife of Croatia, including the molecular phylogenetic analysis of the H gene sequence of field CDV strains circulating in red fox and jackal populations of Croatia. The molecular characterization of hemagglutinin gene genomic regions confirmed the phylogenetic clustering of obtained sequences into the Europa 1 genotype. The obtained CDV red fox sequences were mutually very similar (97.60%). This study indicates the high genetic similarity of Croatian CDV red fox sequences and CDV red fox sequences from Italy and Germany, badger sequences from Germany, polecat sequences from Hungary, and dog sequences from Hungary and Germany.

Survey of SARS-CoV-2 genetic diversity in two major Brazilian cities using a fast and affordable Sanger sequencing strategy

Genetic variants of SARS-CoV-2 have been emerging and circulating in many places across the world. Rapid detection of these variants is essential since their dissemination can impact transmission rates, diagnostic procedures, disease severity, response to vaccines or patient management. Sanger sequencing has been used as the preferred approach for variant detection among circulating human immunodeficiency and measles virus genotypes. Using primers to amplify a fragment of the SARS-CoV-2 genome encoding part of the Spike protein, we showed that Sanger sequencing allowed us to rapidly detect the introduction and spread of three distinct SARS-CoV-2 variants in two major Brazilian cities. In both cities, after the predominance of variants closely related to the virus first identified in China, the emergence of the P.2 variant was quickly followed by the detection of the P1 variant, which became dominant in less than one month after it was first detected.

Canine distemper virus in wildlife in south-western Europe.

Multi-host pathogens emerging and re-emerging at the wildlife-domestic animal interface affect wildlife management and conservation. This is the case of canine distemper virus (CDV), a paramyxovirus closely related to human measles virus and rinderpest virus of cattle. With an area of 10,603 km2 , Asturias region in Atlantic Spain is a hotspot of carnivore diversity, which includes the largest Eurasian brown bear (Ursus arctos arctos) population and one of the largest wolf (Canis lupus) populations in south-western Europe. In 2020-2021, we recorded mortality due to distemper in four carnivore species including three mustelids (Eurasian badger Meles meles, European marten Martes martes and European polecat Mustela putorius) and one canid (red fox, Vulpes vulpes). Clinical signs and pathology were similar across species and consistent with the emergence of a highly pathogenic viral strain, with CDV antigen mainly located in the central nervous system, lungs, spleen and lymph nodes. A molecular study in eight wild carnivore species, also including the Iberian wolf, Eurasian brown bear, American mink (Neovison vison) and stone marten (Martes foina), revealed 19.51% (16/82) of positivity. Phylogenetic analysis demonstrated that CDV belonged to the previously described European lineage. A retrospective serosurvey (2008-2020) showed a high seroprevalence of CDV antibodies (43.4%) in 684 analyzed badgers, indicating a long-term though not stable viral circulation in this multi-host community. The possible triggers of the 2020-2021 outbreak and the implications for carnivore management and conservation are discussed.

Cryo-EM structure of the cetacean morbillivirus nucleoprotein-RNA complex

Cetacean morbillivirus (CeMV) is an emerging and highly infectious paramyxovirus that causes outbreaks in cetaceans and occasionally in pinnipeds, representing a major threat to biodiversity and conservation of endangered marine mammal populations in both hemispheres. As for all non-segmented, negative-sense, single-stranded RNA (ssRNA) viruses, the morbilliviral genome is enwrapped by thousands of nucleoprotein (N) protomers. Each bound to six ribonucleotides, N protomers assemble to form a helical ribonucleoprotein (RNP) complex that serves as scaffold for nucleocapsid formation and as template for viral replication and transcription. While the molecular details on RNP complexes elucidated in human measles virus (MeV) served as paradigm model for these processes in all members of the Morbillivirus genus, no structural information has been obtained from other morbilliviruses, nor has any CeMV structure been solved so far. We report the structure of the CeMV RNP complex, reconstituted in vitro upon binding of recombinant CeMV N to poly-adenine ssRNA hexamers and solved to 4.0 Å resolution by cryo-electron microscopy. In spite of the amino acid sequence similarity and consequently similar folding of the N protomer, the CeMV RNP complex exhibits different helical parameters as compared to previously reported MeV orthologs. The CeMV structure reveals exclusive interactions leading to more extensive protomer-RNA and protomer-protomer interfaces. We identified twelve residues, among those varying between CeMV strains, as putatively important for the stabilization of the RNP complex, which highlights the need to study the potential of CeMV N mutations that modulate nucleocapsid assembly to also affect viral phenotype and host adaptation.

Antiviral Screen against Canine Distemper Virus-Induced Membrane Fusion Activity.

Canine distemper virus (CDV), a close relative of the human pathogen measles virus (MeV), is an enveloped, negative sense RNA virus that belongs to the genus Morbillivirus and causes severe diseases in dogs and other carnivores. Although the vaccination is available as a preventive measure against the disease, the occasional vaccination failure highlights the importance of therapeutic alternatives such as antivirals against CDV. The morbilliviral cell entry system relies on two interacting envelope glycoproteins: the attachment (H) and fusion (F) proteins. Here, to potentially discover novel entry inhibitors targeting CDV H, F and/or the cognate receptor: signaling lymphocyte activation molecule (SLAM) proteins, we designed a quantitative cell-based fusion assay that matched high-throughput screening (HTS) settings. By screening two libraries of small molecule compounds, we successfully identified two membrane fusion inhibitors (F2736-3056 and F2261-0043). Although both inhibitors exhibited similarities in structure and potency with the small molecule compound 3G (an AS-48 class morbilliviral F-protein inhibitor), F2736-3056 displayed improved efficacy in blocking fusion activity when a 3G-escape variant was employed. Altogether, we present a cell-based fusion assay that can be utilized not only to discover antiviral agents against CDV but also to dissect the mechanism of morbilliviral-mediated cell-binding and cell-to-cell fusion activity.

Orally efficacious broad-spectrum allosteric inhibitor of paramyxovirus polymerase.

Paramyxoviruses such as human parainfluenza virus type-3 (HPIV3) and measles virus (MeV) are a substantial health threat. In a high-throughput screen for inhibitors of HPIV3, a major cause of acute respiratory infection, we identified GHP-88309, a non-nucleoside inhibitor of viral polymerase activity that possesses unusual broad-spectrum activity against diverse paramyxoviruses including respiroviruses (i.e. HPIV1 and HPIV3) and morbilliviruses (i.e. MeV). Resistance profiles of distinct target viruses overlap spatially, revealing a conserved binding site in the central cavity of the viral polymerase (L) protein that was validated by photoaffinity labeling-based target mapping. Mechanistic characterization through viral RNA profiling and in vitro MeV polymerase assays identified a block in the initiation phase of the viral polymerase. GHP-88309 showed nanomolar potency against HPIV3 isolates in well-differentiated human airway organoid cultures, was well-tolerated (selectivity index >7,111), orally bioavailable, and provided complete protection against lethal infection in a Sendai virus (SeV)-mouse surrogate model of human HPIV3 disease when administered therapeutically 48 hours after infection. Recoverees had acquired robust immunoprotection against reinfection and viral resistance coincided with severe attenuation. This study provides proof-of-feasibility of a well-behaved broad-spectrum allosteric antiviral and describes a chemotype with high therapeutic potential that addresses major obstacles of anti-paramyxovirus drug development.

Strong antigen-specific T-cell immunity induced by a recombinant human TERT measles virus vaccine and amplified by a DNA/viral vector prime boost in IFNAR/CD46 mice.

Cancer immunotherapy is seeing an increasing focus on vaccination with tumor-associated antigens (TAAs). Human telomerase (hTERT) is a TAA expressed by most tumors to overcome telomere shortening. Tolerance to hTERT can be easily broken both naturally and experimentally and hTERT DNA vaccine candidates have been introduced in clinical trials. DNA prime/boost strategies have been widely developed to immunize efficiently against infectious diseases. We explored the use of a recombinant measles virus (MV) hTERT vector to boost DNA priming as recombinant live attenuated measles virus has an impressive safety and efficacy record. Here, we show that a MV-TERT vector can rapidly and strongly boost DNA hTERT priming in MV susceptible IFNAR/CD46 mouse models. The cellular immune responses were Th1 polarized. No humoral responses were elicited. The 4kb hTERT transgene did not impact MV replication or induction of cell-mediated responses. These findings validate the MV-TERT vector to boost cell-mediated responses following DNA priming in humans.

Enamel Hypoplasia In Canine Distemper Recovered Pup : A Case Report

Canine Distemper (CD) is a severe life threatening disease with a worldwide distribution caused by a Morbillivirus of the family Paramyxoviridae similar to the human Measles virus, transmitted between susceptible hosts and the dog still remains the most important reservoir for the infection (Leisewitz et al., 2001). The disease affects mainly domestic dogs but has become a serious problem in a wide range of hosts, threatening captive and free- ranging wildlife populations including several marine mammals such as seals, dolphins and whales (Visser et al., 1993). Dogs show signs of severe tooth enamel damage or enamel hypoplasia during the course of the disease particularly in young puppies whose teeth have not fully developed

Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

Screening of peste des petits ruminants virus in a population of district Khairpur, Pakistan.

Goats are the Pakistan's fastest growing ruminants, and Pakistan is the third largest goat producer in the world after India and China. Goat meat preference is the main reason for its increased demand. In the country, there are 25 goat breeds and two wild relatives such as Mark and Goats. At present, Pakistan has 53.8 million goats, according to the 2006 GOP report, and their population growth rate was more than 3% per year (37, 23, 22, and 18% of the goat population in Punjab, Sindh, Balochistan, and NWFP, respectively). Peste des petits ruminants virus (PPRV) belongs to the family Paramyxoviridae and is considered to be one of the major constraints on increasing the productivity of goats and sheep in the areas where they exist and become local. It is closely related to cattle and buffalo rinderpest virus, dogs and other wild predator distemper virus, human measles virus, and marine mammalian measles virus. The present study aimed to determine the screening of the PPRV, Capra Hircus Lin. population, in the Khairpur Mirs District, Sindh, Pakistan. We selected 290 goats for serum sample collection and analysis using competitive ELISA kits according to the manufacturer's instructions. Our results showed that 59 (64%) of the 92 clinical cases were positive and 33 (36%) were seronegative. The study concluded that PPR might be more prevalent in the Khairpur District. Furthermore, it is highly recommended to use homologous PPR-attenuated vaccines to prevent lethal virus attacks that control PPR in the country.

Simultaneous virus identification and characterization of severe unexplained pneumonia cases using a metagenomics sequencing technique

Many viruses can cause respiratory diseases in humans. Although great advances have been achieved in methods of diagnosis, it remains challenging to identify pathogens in unexplained pneumonia (UP) cases. In this study, we applied next-generation sequencing (NGS) technology and a metagenomic approach to detect and characterize respiratory viruses in UP cases from Guizhou Province, China. A total of 33 oropharyngeal swabs were obtained from hospitalized UP patients and subjected to NGS. An unbiased metagenomic analysis pipeline identified 13 virus species in 16 samples. Human rhinovirus C was the virus most frequently detected and was identified in seven samples. Human measles virus, adenovirus B 55 and coxsackievirus A10 were also identified. Metagenomic sequencing also provided virus genomic sequences, which enabled genotype characterization and phylogenetic analysis. For cases of multiple infection, metagenomic sequencing afforded information regarding the quantity of each virus in the sample, which could be used to evaluate each viruses’ role in the disease. Our study highlights the potential of metagenomic sequencing for pathogen identification in UP cases.

Oncolytic Virotherapy in Multiple Myeloma: A Possible Alternative Role of Bovine Viruses.

Multiple Myeloma (MM) is a plasma cell malignancy characterized by the tight dependence to the bone marrow (BM) microenvironment that supports MM cells survival. Despite significant therapeutic progress in the recent years with the introduction of several new drugs, MM remains an incurable disease. Oncolytic virotherapy is an alternative therapeutic technology in the cancer treatment exploiting naturally or genetically engineered viruses able to infect, transduce and consequently kill cancer cells directly or indirectly through the delivery of the microenvironment cells. Several oncolytic viruses have shown promising pre-clinical results for the treatment of MM, in particular Measles virus and Reovirus. However, the use of human viruses such as Measles could be limited by the antiviral immune response of the patients due to vaccination or natural infection. In order to avoid these potential limits of the human viruses, the aim of this study was to investigate the development of bovine viruses as an alternative oncolytic strategy in MM by checking these viruses that showed an anti-tumoral activity in different solid tumors. Thus, we investigated the potential lytic effect on human MM cells of the Bovine Viral Diarrhea Virus (BVDV), known to bind CD46 as reported for human measles virus, and the Oncolytic Bovine Herpesvirus type 4 (BoHV-4).Firstly, we treated several human myeloma cell lines (HMCLs) with BVDV or the heat-inactivated virus for 24, 48 and 72 hours. The infection efficiency was verified by nested multiplex PCR. We showed a significant increase of cell mortality, checked by trypan blue count and flow cytometry analysis, already after 48 hours of infection in JJN3 (mean±SD % of dead cells: BVDV 45±11 % vs inactive virus 16±2.5 %, p=0.013), and in OPM2 (BVDV 43±1.4 % vs inactive virus 28±2.1 %, p= 0.015) but not in U266 (BVDV 25±23 % vs inactive virus 18±12 %, p=NS. However, BVDV pre-treatment for 12 hours and followed by 48 hours bortezomib (bor) treatment (concentration ranging: 5-10nM) significantly restored bor sensitivity in U266 resistant cells (mean±SD % of dead cells: BVDV plus bor 10 nM 69±8 % vs inactive virus + bor 10 nM 36±1 %, p= 0.031). Interestingly, the cytotoxic effect of BVDV treatment in HMCLs was associated by a significantly increase of apoptotic markers evaluated by flow cytometry. Subsequently, we infected BM primary purified CD138+, showing a significant increase of the mortality rate after treatment with BVDV as compared to the inactivated virus. On the contrary, BVDV was not able to infect human BM mesenchymal stromal cells (MSCs) not showing any lytic effect.Thereafter the capacity to induce MM cell lysis by a recombinant BoHV-4 virus, delivering a Red Fluorescent Protein (RFP) expression cassette as reporter gene, was also evaluated. As observed by the percentage of RFP-positive cells, BoHV-4 was unable to infect and consequently to kill several HMCLs tested. Then we used BM MSCs as in vitro model for oncolytic virus delivery in co-culture systems with MM cells. BoHV-4 infected hTERT-MSCs, expressing RFP at 24, 48 and 72 hours. Consistently, hTERT-MSCs viability was progressively reduced at 24 and 48 hours after infection, as compared to controls, (mean±SD % reduction of cell viability: -22±8 %, p=0.0254 and -49±2 %, p=0.0001, respectively), reaching the highest effect at 72 hours (-70±1.5 %, p=0.0003). Thus we evaluated the effect of BoHV-4 in a co-culture system between human MSCs and two stroma-dependent HMCLs as INA-6 and saMMi. In both cases the percentage of dead HMCLs increased in co-culture with BoHV-4 infected hTERT-MSCs, as compared to hTERT-MSCs untreated controls (INA-6: BoHV-4 61±2.1 % vs control 12±2.1 %, p= 0.0018; saMMi: BoHV-4 48±1.9 % vs control 14±1.4 %, p= 0.0027).Overall our data indicate both direct and MSC-mediated oncolytic effects of bovine viruses on MM cell, suggesting their possible use as novel alternative anti-MM virotherapy strategy. DisclosuresGiuliani:Celgene: Research Funding; Janssen: Research Funding.

Reduced angiogenic gene expression in morbillivirus-triggered oncolysis in a translational model for histiocytic sarcoma.

Histiocytic sarcoma represents a rare malignant tumour with a short survival time, indicating the need of novel treatment strategies including oncolytic virotherapy. The underlying molecular mechanisms of viral oncolysis are largely unknown. As cancer in companion animals shares striking similarities with human counterparts, we chose a permanent canine histiocytic sarcoma cell line (DH82 cells) to identify global transcriptome changes following infection with canine distemper virus (CDV), a paramyxovirus closely related to human measles virus. Microarray analysis identified 3054 differentially expressed probe sets (DEPs), encoding for 892 up‐ and 869 down‐regulated unique canine genes, respectively, in DH82 cells persistently infected with the vaccine strain Onderstepoort of CDV (DH82‐Ond‐pi), compared to non‐infected DH82 cells. Up‐regulated genes were predominantly related to immune processes, as demonstrated by functional enrichment analysis. Moreover, there was substantial enrichment of genes characteristic for classically activated M1 and alternatively activated M2 macrophages in DH82‐Ond‐pi; however, significant polarization into either of both categories was lacking. ‘Angiogenesis’ was the dominant enriched functional term for the down‐regulated genes, highlighting decreased blood vessel generation as a potential mechanism of paramyxovirus‐induced oncolysis in DH82 cells. The anti‐angiogenic effect of infection was verified by immunohistochemistry, which revealed a lower blood vessel density in an in vivo mouse model, xenotransplanted with DH82‐Ond‐pi, compared to mice transplanted with non‐infected DH82 cells. Reduction in angiogenesis appears to be an important oncolytic mechanism of CDV in DH82 cells, suggesting that similar mechanisms might account for human histiocytic sarcoma and maybe other tumours in conjunction with measles virus.

Histopathologic identification and pattern recognition of common viral infections in the general pathology practice: An illustrated review

Pattern recognition and cytologic features remain essential diagnostic tools in pathology. Viral cytopathic effect may be the first clue to a diagnosis of a viral infection. This paper aims to provide a brief illustrated summary of the histopathologic changes caused by commonly encountered and rare viruses. The list of viruses discussed with characteristic viral inclusions or distinctive cytopathic effect includes cytomegalovirus, adenovirus, herpes virus (herpes simplex virus and varicella zoster virus), human papillomavirus, respiratory syncytial virus, parvovirus, poxvirus (molluscum contagiosum virus), and polyoma virus (JC virus and BK virus). Also reviewed are the characteristic histologic and cytopathic changes for Epstein-Barr virus (EBV), Paramyxoviruses (human parainfluenza virus and measles virus), human immunodeficiency virus (HIV), and hepatitis B virus.

Function and expression of CD1d and invariant natural killer T-cell receptor in the cotton rat (Sigmodon hispidus).

The cotton rat (Sigmodon hispidus) belongs to the rodent family of Cricetidae and provides a powerful model to study the pathogenesis of human respiratory viruses and measles virus. Recent studies in other rodent models have suggested a role for invariant natural killer T (iNKT) cells in antiviral immunity and vaccination against respiratory virus infections. Using new experimental tools, we provide the first evidence for a functional CD1d cell molecule (crCD1d) and iNKT T-cell receptor in cotton rats. The crCD1d cDNA sequence was identified and crCD1d transductants showed that monoclonal antibody WTH-2 stains crCD1d as efficiently as mouse or rat CD1d. The expression of crCD1d was clearly weaker for thymocytes and B cells, and higher for T cells, which is different to what is found in murine species. The antigen-presenting capacity of crCD1d was demonstrated with crCD1d-immunoglobulin dimers loaded with the glycolipid PBS57, which bound iNKT T-cell receptors. Evidence for functional cotton rat iNKT cells was provided by detection of interferon-γ and interleukin-4 in cultures of splenocytes stimulated with PBS57 and α-galactosylceramide and by specific staining of about 0·2% of splenocytes with PBS57-loaded crCD1d dimers. Canonical AV14/AJ18 rearrangements were identified and found to contain multiple members of the AV14 (AV11) family. One of them was expressed and found to bind CD1d dimers. In summary, these data provide the first evidence for functional CD1d molecules and iNKT T-cell receptors in cotton rats and provide the tools to analyse them both in the cotton rat model of infectious diseases.

Human and Canine Codon Optimization of Measles and Canine Distemper Viral Nucleic Acid Sequences Increases Sequence Identity and Protein Expression Compared to Wild Type and Human Codon Sub‐Optimized Constructs

The role of codon usage bias (CUB) in the host adaptation and pathogenicity of human measles virus (HMV) and canine distemper virus (CDV) is being investigated and compared. Analysis of nucleic acid sequences for HMV and CDV nucleoprotein (N) revealed that human and canine CUB optimized constructs, as compared to wild type (WT) and human CUB sub‐optimized constructs, were characterized by increased nucleic acid and codon identities, and increased protein expression when transfected into human (293 HEK) cells. The purpose of this study was to characterize human and canine codon optimized nucleic acid sequences of the MHV and CDV F, M, H,L and P/C proteins. All human and canine CUB optimized HMV and CDV nucleic acid sequences had increased nucleic acid and codon identity as compared to WT sequences. Protein expression in human cells transfected with human and canine CUB optimized constructs of the F, M, H and P/C proteins was assessed using florescence, Cellomic and where possible western analysis. Higher protein expression was present in cells transfected with the human and canine codon optimized constructs compared to cells transfected with HMV and CDV WT or HMV suboptimized constructs. These results suggest that further adaptation of HMV and CDV to the mammalian CUB could enhance viral protein expression and pathogenesis.

Outbreak of coinfection with human metapneumovirus and measles virus resulting in the death of a child at a hospital in China

Two children with different digestive diseases were admitted to the gastroenterology department of a children's hospital in Hangzhou, Zhejiang Province, China, in May 2010. They manifested successively acute lower respiratory tract infection symptoms during their stay in the hospital. The epidemiologic and experimental evidence supports that one child acquired nosocomial coinfection with measles virus and human metapneumovirus from another child while they shared the same ward.

Measles fusion machinery is dysregulated in neuropathogenic variants.

ABSTRACTParamyxoviruses, including the human pathogen measles virus (MV), enter host cells by fusing their viral envelope with the target cell membrane. This fusion process is driven by the concerted actions of the two viral envelope glycoproteins, the receptor binding protein (hemagglutinin [H]) and the fusion (F) protein. H attaches to specific proteinaceous receptors on host cells; once the receptor engages, H activates F to directly mediate lipid bilayer fusion during entry. In a recent MV outbreak in South Africa, several HIV-positive people died of MV central nervous system (CNS) infection. We analyzed the virus sequences from these patients and found that specific intrahost evolution of the F protein had occurred and resulted in viruses that are “CNS adapted.” A mutation in F of the CNS-adapted virus (a leucine-to-tryptophan change present at position 454) allows it to promote fusion with less dependence on engagement of H by the two known wild-type (wt) MV cellular receptors. This F protein is activated independently of H or the receptor and has reduced thermal stability and increased fusion activity compared to those of the corresponding wt F. These functional effects are the result of the single L454W mutation in F. We hypothesize that in the absence of effective cellular immunity, such as HIV infection, MV variants bearing altered fusion machinery that enabled efficient spread in the CNS underwent positive selection.