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1.
Viruses ; 14(7)2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35891503

RESUMO

Nipah virus (NiV) is a zoonotic paramyxovirus with a fatality rate of up to 92% in humans. While several pathogenic mechanisms used by NiV to counteract host immune defense responses have been described, all of the processes that take place in cells during infection are not fully characterized. Here, we describe the formation of ordered intracellular structures during NiV infection. We observed that these structures are formed specifically during NiV infection, but not with other viruses from the same Mononegavirales order (namely Ebola virus) or from other orders such as Bunyavirales (Junín virus). We also determined the kinetics of the appearance of these structures and their cellular localization at the cellular periphery. Finally, we confirmed the presence of these NiV-specific ordered structures using structured illumination microscopy (SIM), as well as their localization by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and correlative light and electron microscopy (CLEM). Herein, we describe a cytopathogenic mechanism that provides a new insight into NiV biology. These newly described ordered structures could provide a target for novel antiviral approaches.


Assuntos
Ebolavirus , Infecções por Henipavirus , Vírus Nipah , Paramyxovirinae , Antivirais , Humanos , Vírus Nipah/fisiologia
2.
Viruses ; 14(6)2022 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-35746749

RESUMO

Ecological and experimental infection studies have identified Egyptian rousette bats (ERBs; Rousettus aegyptiacus: family Pteropodidae) as a reservoir host for the zoonotic rubula-like paramyxovirus Sosuga virus (SOSV). A serial sacrifice study of colony-bred ERBs inoculated with wild-type, recombinant SOSV identified small intestines and salivary gland as major sites of viral replication. In the current study, archived formalin-fixed paraffin-embedded (FFPE) tissues from the serial sacrifice study were analyzed in depth-histologically and immunohistochemically, for SOSV, mononuclear phagocytes and T cells. Histopathologic lesion scores increased over time and viral antigen persisted in a subset of tissues, indicating ongoing host responses and underscoring the possibility of chronic infection. Despite the presence of SOSV NP antigen and villus ulcerations in the small intestines, there were only mild increases in mononuclear phagocytes and T cells, a host response aligned with disease tolerance. In contrast, there was a statistically significant, robust and targeted mononuclear phagocyte cell responses in the salivary glands at 21 DPI, where viral antigen was sparse. These findings may have broader implications for chiropteran-paramyxovirus interactions, as bats are hypothesized to be the ancestral hosts of this diverse virus family and for ERB immunology in general, as this species is also the reservoir host for the marburgviruses Marburg virus (MARV) and Ravn virus (RAVV) (family Filoviridae).


Assuntos
Quirópteros , Marburgvirus , Paramyxovirinae , Vírus não Classificados , Animais , Antígenos Virais , Vírus de DNA , Marburgvirus/fisiologia , Tropismo
3.
Viruses ; 14(5)2022 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-35632848

RESUMO

Paramyxoviridae is a viral family within the order of Mononegavirales; they are negative single-strand RNA viruses that can cause significant diseases in both humans and animals. In order to replicate, paramyxoviruses-as any other viruses-have to bypass an important protective mechanism developed by the host's cells: the defensive line driven by interferon. Once the viruses are recognized, the cells start the production of type I and type III interferons, which leads to the activation of hundreds of genes, many of which encode proteins with the specific function to reduce viral replication. Type II interferon is produced by active immune cells through a different signaling pathway, and activates a diverse range of genes with the same objective to block viral replication. As a result of this selective pressure, viruses have evolved different strategies to avoid the defensive function of interferons. The strategies employed by the different viral species to fight the interferon system include a number of sophisticated mechanisms. Here we analyzed the current status of the various strategies used by paramyxoviruses to subvert type I, II, and III interferon responses.


Assuntos
Paramyxovirinae , Vírus de RNA , Animais , Antivirais , Interferon gama , Interferons , Paramyxoviridae/genética , Vírus de RNA/genética , Replicação Viral
4.
Viruses ; 14(1)2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-35062341

RESUMO

Particles of many paramyxoviruses include small amounts of proteins with a molecular weight of about 20 kDa. These proteins, termed "C", are basic, have low amino acid homology and some secondary structure conservation. C proteins are encoded in alternative reading frames of the phosphoprotein gene. Some viruses express nested sets of C proteins that exert their functions in different locations: In the nucleus, they interfere with cellular transcription factors that elicit innate immune responses; in the cytoplasm, they associate with viral ribonucleocapsids and control polymerase processivity and orderly replication, thereby minimizing the activation of innate immunity. In addition, certain C proteins can directly bind to, and interfere with the function of, several cytoplasmic proteins required for interferon induction, interferon signaling and inflammation. Some C proteins are also required for efficient virus particle assembly and budding. C-deficient viruses can be grown in certain transformed cell lines but are not pathogenic in natural hosts. C proteins affect the same host functions as other phosphoprotein gene-encoded proteins named V but use different strategies for this purpose. Multiple independent systems to counteract host defenses may ensure efficient immune evasion and facilitate virus adaptation to new hosts and tissue environments.


Assuntos
Imunidade Inata/imunologia , Infecções por Paramyxoviridae/imunologia , Paramyxovirinae/fisiologia , Fosfoproteínas/imunologia , Proteínas Virais/imunologia , Replicação Viral/fisiologia , Animais , Genoma Viral , Humanos , Evasão da Resposta Imune , Inflamassomos , Fases de Leitura Aberta , Paramyxovirinae/genética , Fosfoproteínas/química , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Filogenia , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo , Montagem de Vírus
5.
Zoonoses Public Health ; 69(2): 117-135, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34817117

RESUMO

Bat paramyxoviruses (PmV) are a diverse group of viruses and include zoonotic viruses such as henipaviruses. Members of this group in other continents have been associated with severe respiratory and neurological infections in animals and humans. Furthermore, despite the richness of diverse bat species that can transmit this virus in African countries like Nigeria, there is very scanty information as to the presence and co-evolution of paramyxoviruses in bats. There is a need for continuous surveillance of zoonotic viruses and their biological reservoirs as this will help in the prevention and management of pathogens' spillovers. This study detected novel paramyxoviruses in Chaerephon nigeriae bat species found in Badagry, Lagos. Phylogenetic analyses of paramyxovirus sequences' co-evolution with frugivorous and insectivorous bats circulating in African countries were also performed using sequences of African origin available in the Database of Bat-Associated Viruses (DBatVir: http://www.mgc.ac.cn/DBatVir/). Oral swabs (n = 18) and blood samples (n = 32) were collected from C. nigeriae bats in Badagry, Lagos. The L gene of bat paramyxovirus was detected in all oral swabs using PCR techniques. Six of the amplicons were successfully sequenced. Estimated phylogenies placed the sequences in close relationship with those isolated from insectivorous bats. Phylogenetic analyses of previously sequenced isolates in the African region showed the likelihood of different co-evolution mechanisms of paramyxoviruses with frugivorous bats compared with insectivorous bats. This may be due to codon usage bias of the L gene. Spatial distribution of paramyxoviruses in African countries showed limited ongoing surveillance of this virus in the continent, especially in southern and northern countries. Extensive surveillance of paramyxoviruses with possible zoonotic potentials among bat species in the continent is recommended. This will provide further insights into co-evolution as well as prevent possible spillover into the human population.


Assuntos
Quirópteros , Paramyxovirinae , Animais , Nigéria/epidemiologia , Paramyxoviridae/genética , Paramyxovirinae/genética , Filogenia
6.
Viruses ; 13(12)2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34960748

RESUMO

All paramyxoviruses, which include the mumps virus, measles virus, Nipah virus, Newcastle disease virus, and Sendai virus, have non-segmented single-stranded negative-sense RNA genomes. These RNA genomes are enwrapped throughout the viral life cycle by nucleoproteins, forming helical nucleocapsids. In addition to these helical structures, recombinant paramyxovirus nucleocapsids may occur in other assembly forms such as rings, clam-shaped structures, and double-headed nucleocapsids; the latter two are composed of two single-stranded helices packed in a back-to-back pattern. In all of these assemblies, the neighboring nucleoprotein protomers adopt the same domain-swapping mode via the N-terminal arm, C-terminal arm, and recently disclosed N-hole. An intrinsically disordered region in the C-terminal domain of the nucleoproteins, called the N-tail, plays an unexpected role in regulating the transition among the different assembly forms that occurs with other viral proteins, especially phosphoprotein. These structures, together with the helical nucleocapsids, significantly enrich the structural diversity of the paramyxovirus nucleocapsids and help explain the functions of these diverse assemblies, including RNA genome protection, transcription, and replication, as well as encapsulation.


Assuntos
Proteínas do Nucleocapsídeo/química , Nucleocapsídeo/química , Paramyxovirinae/química , Modelos Moleculares , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/metabolismo , Paramyxovirinae/classificação , Paramyxovirinae/genética , Conformação Proteica , Domínios Proteicos , Estrutura Quaternária de Proteína , Subunidades Proteicas/química
7.
Viruses ; 13(12)2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34960734

RESUMO

Viruses of the Paramyxoviridae family share a common and complex molecular machinery for transcribing and replicating their genomes. Their non-segmented, negative-strand RNA genome is encased in a tight homopolymer of viral nucleoproteins (N). This ribonucleoprotein complex, termed a nucleocapsid, is the template of the viral polymerase complex made of the large protein (L) and its co-factor, the phosphoprotein (P). This review summarizes the current knowledge on several aspects of paramyxovirus transcription and replication, including structural and functional data on (1) the architecture of the nucleocapsid (structure of the nucleoprotein, interprotomer contacts, interaction with RNA, and organization of the disordered C-terminal tail of N), (2) the encapsidation of the genomic RNAs (structure of the nucleoprotein in complex with its chaperon P and kinetics of RNA encapsidation in vitro), and (3) the use of the nucleocapsid as a template for the polymerase complex (release of the encased RNA and interaction network allowing the progress of the polymerase complex). Finally, this review presents models of paramyxovirus transcription and replication.


Assuntos
Nucleocapsídeo/química , Paramyxovirinae/metabolismo , Regulação Viral da Expressão Gênica , Humanos , Nucleocapsídeo/genética , Nucleocapsídeo/metabolismo , Proteínas do Nucleocapsídeo/química , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/metabolismo , Infecções por Paramyxoviridae/virologia , Paramyxovirinae/química , Paramyxovirinae/classificação , Paramyxovirinae/genética , Filogenia , RNA Viral/química , RNA Viral/genética , RNA Viral/metabolismo
8.
Viruses ; 13(10)2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34696450

RESUMO

Paramyxoviruses, negative-sense single-stranded RNA viruses, pose a critical threat to human public health. Currently, 78 species, 17 genera, and 4 subfamilies of paramyxoviruses are harbored by multiple natural reservoirs, including rodents, bats, birds, reptiles, and fish. Henipaviruses are critical zoonotic pathogens that cause severe acute respiratory distress and neurological diseases in humans. Using reverse transcription-polymerase chain reaction, 115 Crocidura species individuals were examined for the prevalence of paramyxovirus infections. Paramyxovirus RNA was observed in 26 (22.6%) shrews collected at five trapping sites, Republic of Korea. Herein, we report two genetically distinct novel paramyxoviruses (genus: Henipavirus): Gamak virus (GAKV) and Daeryong virus (DARV) isolated from C. lasiura and C. shantungensis, respectively. Two GAKVs and one DARV were nearly completely sequenced using next-generation sequencing. GAKV and DARV contain six genes (3'-N-P-M-F-G-L-5') with genome sizes of 18,460 nucleotides and 19,471 nucleotides, respectively. The phylogenetic inference demonstrated that GAKV and DARV form independent genetic lineages of Henipavirus in Crocidura species. GAKV-infected human lung epithelial cells elicited the induction of type I/III interferons, interferon-stimulated genes, and proinflammatory cytokines. In conclusion, this study contributes further understandings of the molecular prevalence, genetic characteristics and diversity, and zoonotic potential of novel paramyxoviruses in shrews.


Assuntos
Henipavirus/classificação , Henipavirus/genética , Paramyxovirinae/classificação , Paramyxovirinae/genética , Filogenia , Musaranhos/virologia , Animais , Biodiversidade , Aves/virologia , Quirópteros/virologia , Peixes/virologia , Henipavirus/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Interferons , Paramyxovirinae/isolamento & purificação , Vírus de RNA/classificação , Répteis/virologia , República da Coreia , Roedores/virologia , Zoonoses Virais/virologia
9.
J Virol ; 95(22): e0132121, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34469242

RESUMO

H5N1, an avian influenza virus, is known to circulate in many Asian countries, such as Bangladesh, China, Cambodia, Indonesia, and Vietnam. The current FDA-approved H5N1 vaccine has a moderate level of efficacy. A safe and effective vaccine is needed to prevent outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in humans. Nonsegmented negative-sense single-stranded viruses (NNSVs) are widely used as a vector to develop vaccines for humans, animals, and poultry. NNSVs stably express foreign genes without integrating with the host genome. J paramyxovirus (JPV) is a nonsegmented negative-strand RNA virus and a member of the proposed genus Jeilongvirus in the family Paramyxoviridae. JPV-specific antibodies have been detected in rodents, bats, humans, and pigs, but the virus is not associated with disease in any species other than mice. JPV replicates in the respiratory tract of mice and efficiently expresses the virus-vectored foreign genes in tissue culture cells. In this work, we explored JPV as a vector for developing an H5N1 vaccine using intranasal delivery. We incorporated hemagglutinin (HA) of H5N1 into the JPV genome by replacing the small hydrophobic (SH) gene to generate a recombinant JPV expressing HA (rJPV-ΔSH-H5). A single intranasal administration of rJPV-ΔSH-H5 protected mice from a lethal HPAI H5N1 challenge. Intranasal vaccination of rJPV-ΔSH-H5 in rhesus macaques elicited antigen-specific humoral and cell-mediated immune responses. This work demonstrates that JPV is a promising vaccine vector. IMPORTANCE A highly pathogenic avian influenza (HPAI) H5N1 outbreak in Southeast Asia destroyed millions of birds. Transmission of H5N1 into humans resulted in deaths in many countries. In this work, we developed a novel H5N1 vaccine candidate using J paramyxovirus (JPV) as a vector and demonstrated that JPV is an efficacious vaccine vector in animals. Nonsegmented negative-sense single-stranded viruses (NNSVs) stably express foreign genes without integrating into the host genome. JPV, an NNSV, replicates efficiently in the respiratory tract and induces robust immune responses.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Paramyxovirinae/imunologia , Animais , Linhagem Celular , Chlorocebus aethiops , Cricetinae , Cães , Feminino , Humanos , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos BALB C
10.
Viruses ; 13(8)2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34452518

RESUMO

The straw-coloured fruit bat (Eidolon helvum) is widespread in sub-Saharan Africa and is widely hunted for bushmeat. It is known to harbour a range of paramyxoviruses, including rubuloviruses and henipaviruses, but the zoonotic potential of these is unknown. We previously found a diversity of paramyxoviruses within a small, captive colony of E. helvum after it had been closed to contact with other bats for 5 years. In this study, we used under-roost urine collection to further investigate the paramyxovirus diversity and ecology in this colony, which had been closed to the outside for 10 years at the time of sampling. By sampling urine weekly throughout an entire year, we investigated possible seasonal patterns of shedding of virus or viral RNA. Using a generic paramyxovirus L-gene PCR, we detected eight distinct paramyxovirus RNA sequences. Six distinct sequences were detected using a Henipavirus-specific PCR that targeted a different region of the L-gene. Sequence detection had a bi-annual pattern, with the greatest peak in July, although different RNA sequences appeared to have different shedding patterns. No significant associations were detected between sequence detection and birthing season, environmental temperature or humidity, and no signs of illness were detected in any of the bats in the colony during the period of sample collection.


Assuntos
Quirópteros/urina , Quirópteros/virologia , Paramyxovirinae/metabolismo , RNA Viral/metabolismo , Animais , Reservatórios de Doenças/virologia , Paramyxovirinae/classificação , Paramyxovirinae/genética , Paramyxovirinae/isolamento & purificação , RNA Viral/genética , Estações do Ano , Urina/virologia , Eliminação de Partículas Virais
11.
Viruses ; 13(8)2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34452523

RESUMO

Bats have been identified as the natural hosts of several emerging zoonotic viruses, including paramyxoviruses, such as Hendra and Nipah viruses, that can cause fatal disease in humans. Recently, African fruit bats with populations that roost in or near urban areas have been shown to harbour a great diversity of paramyxoviruses, posing potential spillover risks to public health. Understanding the circulation of these viruses in their reservoir populations is essential to predict and prevent future emerging diseases. Here, we identify a high incidence of multiple paramyxoviruses in urine samples collected from a closed captive colony of circa 115 straw-coloured fruit bats (Eidolon helvum). The sequences detected have high nucleotide identities with those derived from free ranging African fruit bats and form phylogenetic clusters with the Henipavirus genus, Pararubulavirus genus and other unclassified paramyxoviruses. As this colony had been closed for 5 years prior to this study, these results indicate that within-host paramyxoviral persistence underlies the role of bats as reservoirs of these viruses.


Assuntos
Quirópteros/virologia , Reservatórios de Doenças/virologia , Paramyxovirinae/fisiologia , Animais , Quirópteros/crescimento & desenvolvimento , Quirópteros/urina , Feminino , Masculino , Paramyxovirinae/classificação , Paramyxovirinae/genética , Paramyxovirinae/isolamento & purificação , Filogenia , Urina/virologia
12.
BMC Ecol Evol ; 21(1): 148, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34325659

RESUMO

BACKGROUND: Bat-borne viruses are relatively host specific. We hypothesize that this host specificity is due to coevolution of the viruses with their hosts. To test this hypothesis, we investigated the coevolution of coronavirus and paramyxovirus with their bat hosts. Published nucleotide sequences of the RNA-dependent RNA polymerase (RdRp) gene of 60 coronavirus strains identified from 37 bat species, the RNA polymerase large (L) gene of 36 paramyxovirus strains from 29 bat species, and the cytochrome B (cytB) gene of 35 bat species were analyzed for coevolution signals. Each coevolution signal detected was tested and verified by global-fit cophylogenic analysis using software ParaFit, PACo, and eMPRess. RESULTS: Significant coevolution signals were detected in coronaviruses and paramyxoviruses and their bat hosts, and closely related bat hosts were found to carry closely related viruses. CONCLUSIONS: Our results suggest that paramyxovirus and coronavirus coevolve with their hosts.


Assuntos
Quirópteros , Infecções por Coronavirus , Coronavirus , Paramyxovirinae , Animais , Coronavirus/genética , Filogenia
13.
Lancet Glob Health ; 9(8): e1077-e1087, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34166626

RESUMO

BACKGROUND: Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age. METHODS: We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570). FINDINGS: 203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome. INTERPRETATION: We report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Saúde Global/estatística & dados numéricos , Infecções por Paramyxoviridae/complicações , Paramyxovirinae/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Pré-Escolar , Humanos , Lactente , Recém-Nascido
14.
Viruses ; 13(4)2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810446

RESUMO

Diverse paramyxoviruses have coevolved with their bat hosts, including fruit bats such as flying foxes (Chiroptera: Pteropodidae). Several of these viruses are zoonotic, but the diversity and distribution of Paramyxoviridae are poorly understood. We screened pooled feces samples from three Pteropus vampyrus colonies and assayed tissues, rectal swabs, and oral swabs from 95 individuals of 23 pteropodid species sampled at 17 sites across the Indonesian archipelago with a conventional paramyxovirus PCR; all tested negative. Samples from 43 individuals were screened with next generation sequencing (NGS), and a single Pteropus vampyrus collected near Flores had Tioman virus sequencing reads. Tioman virus is a bat-borne virus in the genus Pararubulavirus with prior evidence of spillover to humans. This work expands the known range of Tioman virus, and it is likely that this isolated colony likely has sustained intergenerational transmission over a long period.


Assuntos
Quirópteros/virologia , Fezes/virologia , Infecções por Paramyxoviridae/veterinária , Paramyxovirinae/classificação , Paramyxovirinae/genética , Animais , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Indonésia , Infecções por Paramyxoviridae/transmissão , Paramyxovirinae/isolamento & purificação
15.
Infect Genet Evol ; 91: 104809, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33727141

RESUMO

Eurasian collared doves (Streptopelia decaocto) were introduced into Florida in the 1980s and have since established populations throughout the continental United States. Pigeon paramyxovirus-1 (PPMV-1), a species-adapted genotype VI Avian orthoavulavirus 1, has caused periodic outbreaks among collared doves in the U.S. since 2001 with outbreaks occasionally involving native doves. In California, PPMV-1 mortality events were first documented in Riverside County in 2014 with subsequent outbreaks in 23 additional counties from southern to northern California between 2015 and 2019. Affected collared doves exhibited torticollis and partial paralysis. Pale kidneys were frequently visible on gross necropsy (65.4%; 51/78) while lymphoplasmacytic interstitial nephritis often with acute tubular necrosis (96.0%; 24/25) and pancreatic necrosis (80.0%; 20/25) were common findings on histopathology. In total, PPMV-1 was confirmed by rRT-PCR and sequence analysis from oropharyngeal and/or cloacal swabs in 93.0% (40/43) of the collared doves tested from 16 California counties. In 2017, Avian orthoavulavirus 1 was confirmed in a native mourning dove (Zenaida macroura) found dead during a PPMV-1 outbreak in collared doves by rRT-PCR from formalin-fixed paraffin-embedded (FFPE) tissues, after the initial rRT-PCR from swabs failed to detect the virus. Molecular sequencing of the fusion protein of isolates collected from collared doves during outbreaks in 2014, 2016, and 2017 identified two distinct subgenotypes, VIa and VIn. Subgenotype VIn has been primarily isolated from collared doves in the southern U.S., while VIa has been isolated from mixed avian species in the northeastern U.S., indicating two independent introductions into California. While populations of collared doves are not expected to be substantially impacted by this disease, PPMV-1 may pose a threat to already declining populations of native columbids. This threat could be assessed by monitoring native and non-native columbids for PPMV-1. Based on our study, swab samples may not be sufficient to detect infection in native columbids and may require the use of non-traditional diagnostic approaches, such as FFPE tissues, to ensure virus detection.


Assuntos
Doenças das Aves/epidemiologia , Columbidae , Infecções por Paramyxoviridae/veterinária , Paramyxovirinae/isolamento & purificação , Fatores Etários , Animais , Doenças das Aves/mortalidade , Doenças das Aves/virologia , California/epidemiologia , Feminino , Espécies Introduzidas , Masculino , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/mortalidade , Infecções por Paramyxoviridae/virologia , Paramyxovirinae/genética , Prevalência , Estações do Ano , Fatores Sexuais
16.
Am J Trop Med Hyg ; 104(3): 1106-1110, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33534762

RESUMO

Bats are often consumed by some ethnic groups in Nigeria despite association of bats with many important emerging viruses. More than 300 bats representing eight species were captured during 2010-2011 in eight locations of northern Nigeria. Available fecal swabs (n = 95) were screened for the presence of arenaviruses, CoVs, paramyxoviruses (PMVs), reoviruses, rhabdoviruses, and influenza viruses using generic reverse transcription-polymerase chain reaction assays. Here, we document the detection of CoVs, PMVs, reoviruses, and rotaviruses (RVs) in Nigerian bats. The Nigerian bat CoVs are grouped within other bat SARS-CoV-like viruses identified from Ghana in a sister clade next to the human SARS-CoV clade. The phylogenetic analysis indicated a broad range of RVs present in Nigerian bats, some cluster with human RVs and some represent novel species. Our study adds that continuing global surveillance for viruses in bats to understand their origin, adaptation, and evolution is important to prevent and control future zoonotic disease outbreaks.


Assuntos
Quirópteros/virologia , Vírus de RNA/classificação , Vírus de RNA/genética , Viroses/epidemiologia , Viroses/veterinária , Zoonoses/transmissão , Animais , Coronavirus/genética , Coronavirus/isolamento & purificação , Evolução Molecular , Genoma Viral , Humanos , Nigéria , Orthoreovirus Aviário/genética , Orthoreovirus Aviário/isolamento & purificação , Paramyxovirinae/genética , Paramyxovirinae/isolamento & purificação , Filogenia , Filogeografia , Vírus de RNA/isolamento & purificação , Rotavirus/genética , Rotavirus/isolamento & purificação , Zoonoses/epidemiologia
17.
Infect Genet Evol ; 91: 104777, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33631368

RESUMO

As an economically important poultry pathogen, avian paramyxovirus serotype 4 (APMV-4) frequently reported and isolated from domestic and wild birds particularly waterfowls worldwide. However, evolutionary dynamics of APMV-4 based on genomic characteristics is lacking. In this study, APMV-4 strain designated JX-G13 was isolated from oropharyngeal and cloacal swab samples of wild birds in China. Phylogenetic analysis revealed APMV-4 strains were divided into four genetic genotypes and China isolates were mainly clustered into Genotype I. The MCMC tree indicated that APMV-4 diverged about 104 years ago with the evolutionary rate of 1.2927 × 10-3 substitutions/site/year. BSP analysis suggested that the effective population size of APMV-4 exhibited a steady state and decreased slowly after 2013. The F gene of APMV-4 was considered relatively conserved among isolates based on nucleotide diversity analysis. Although the F gene was under purifying selection, two positions (5 and 21) located in 3'-UTR were subject to positive selection. Our study firstly presented the evolutionary assessments on the genetic diversity of circulating APMV-4 from wild birds and domestic poultry.


Assuntos
Doenças das Aves/virologia , Evolução Molecular , Genótipo , Paramyxovirinae/genética , Animais , China , Cloaca/virologia , Orofaringe/virologia , Filogenia
18.
Viruses ; 12(12)2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33276587

RESUMO

The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant disease burden of these viruses is further exacerbated by the limited therapeutics that are currently available. Host cellular proteins that can antagonize or limit virus replication are therefore a promising area of research to identify candidate molecules with the potential for host-targeted therapies. Host proteins known as host cell restriction factors are constitutively expressed and/or induced in response to virus infection and include proteins from interferon-stimulated genes (ISGs). Many ISG proteins have been identified but relatively few have been characterized in detail and most studies have focused on studying their antiviral activities against particular viruses, such as influenza A viruses and human immunodeficiency virus (HIV)-1. This review summarizes current literature regarding host cell restriction factors against paramyxo- and pneumoviruses, on which there is more limited data. Alongside discussion of known restriction factors, this review also considers viral countermeasures in overcoming host restriction, the strengths and limitations in different experimental approaches in studies reported to date, and the challenges in reconciling differences between in vitro and in vivo data. Furthermore, this review provides an outlook regarding the landscape of emerging technologies and tools available to study host cell restriction factors, as well as the suitability of these proteins as targets for broad-spectrum antiviral therapeutics.


Assuntos
Interações Hospedeiro-Patógeno , Infecções por Paramyxoviridae/virologia , Paramyxovirinae/fisiologia , Infecções por Pneumovirus/virologia , Pneumovirus/fisiologia , Animais , Biomarcadores , Regulação Viral da Expressão Gênica , Especificidade de Hospedeiro , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Infecções por Paramyxoviridae/genética , Infecções por Paramyxoviridae/metabolismo , Infecções por Pneumovirus/genética , Infecções por Pneumovirus/metabolismo , Tropismo Viral , Replicação Viral
19.
Front Immunol ; 11: 592370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250897

RESUMO

Prior to 2020, the threat of a novel viral pandemic was omnipresent but largely ignored. Just 12 months prior to the Coronavirus disease 2019 (COVID-19) pandemic our team received funding from the Coalition for Epidemic Preparedness Innovations (CEPI) to establish and validate a rapid response pipeline for subunit vaccine development based on our proprietary Molecular Clamp platform. Throughout the course of 2019 we conducted two mock tests of our system for rapid antigen production against two potential, emerging viral pathogens, Achimota paramyxovirus and Wenzhou mammarenavirus. For each virus we expressed a small panel of recombinant variants of the membrane fusion protein and screened for expression level, product homogeneity, and the presence of the expected trimeric pre-fusion conformation. Lessons learned from this exercise paved the way for our response to COVID-19, for which our candidate antigen is currently in phase I clinical trial.


Assuntos
Desenho de Fármacos , Vacinas de Subunidades , Animais , Arenaviridae , Vacinas contra COVID-19 , Defesa Civil , Ensaios Clínicos como Assunto , Humanos , Estrutura Molecular , Paramyxovirinae/imunologia , Fatores de Tempo , Vacinas de Subunidades/química , Vacinas Virais
20.
Viruses ; 12(11)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143230

RESUMO

Bats are an important source of viral zoonoses, including paramyxoviruses. The paramyxoviral Pararubulavirus genus contains viruses mostly derived from bats that are common, diverse, distributed throughout the Old World, and known to be zoonotic. Here, we describe a new member of the genus Achimota pararubulavirus 3 (AchPV3) and its isolation from the urine of African straw-coloured fruit bats on primary bat kidneys cells. We sequenced and analysed the genome of AchPV3 relative to other Paramyxoviridae, revealing it to be similar to known pararubulaviruses. Phylogenetic analysis of AchPV3 revealed the failure of molecular detection in the urine sample from which AchPV3 was derived and an attachment protein most closely related with AchPV2-a pararubulavirus known to cause cross-species transmission. Together these findings add to the picture of pararubulaviruses, their sources, and variable zoonotic potential, which is key to our understanding of host restriction and spillover of bat-derived paramyxoviruses. AchPV3 represents a novel candidate zoonosis and an important tool for further study.


Assuntos
Quirópteros/virologia , Infecções por Paramyxoviridae/veterinária , Paramyxovirinae/classificação , Filogenia , Animais , Células Cultivadas , Chlorocebus aethiops , Genoma Viral , Rim/citologia , Rim/virologia , Infecções por Paramyxoviridae/urina , Paramyxovirinae/isolamento & purificação , RNA Viral , Células Vero , Sequenciamento Completo do Genoma , Zoonoses/virologia
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