Publications by authors named "Komal Jain"

57 Publications

Viral capture sequencing detects unexpected viruses in the cerebrospinal fluid of adults with meningitis.

J Infect 2022 Jan 3. Epub 2022 Jan 3.

Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK. Electronic address:

Objectives: Many patients with meningitis have no aetiology identified leading to unnecessary antimicrobials and prolonged hospitalisation. We used viral capture sequencing to identify possible pathogenic viruses in adults with community-acquired meningitis.

Methods: Cerebrospinal fluid (CSF) from 73 patients was tested by VirCapSeq-VERT, a probe set designed to capture viral targets using high throughput sequencing. Patients were categorised as suspected viral meningitis - CSF pleocytosis, no pathogen identified (n = 38), proven viral meningitis - CSF pleocytosis with a pathogen identified (n = 15) or not meningitis - no CSF pleocytosis (n = 20).

Results: VirCapSeq-VERT detected virus in the CSF of 16/38 (42%) of those with suspected viral meningitis, including twelve individual viruses. A potentially clinically relevant virus was detected in 9/16 (56%). Unexpectedly Toscana virus, rotavirus and Saffold virus were detected and assessed to be potential causative agents.

Conclusion: VirCapSeq-VERT increases the probability of detecting a virus. Using this agnostic approach we identified Toscana virus and, for the first time in adults, rotavirus and Saffold virus, as potential causative agents in adult meningitis. Further work is needed to determine the prevalence of atypical viral candidates as well as the clinical impact of using sequencing methods in real time. This knowledge can help to reduce antimicrobial use and hospitalisations leading to both patient and health system benefits.
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http://dx.doi.org/10.1016/j.jinf.2021.12.042DOI Listing
January 2022

Facile Synthesis, Static, and Dynamic Magnetic Characteristics of Varying Size Double-Surfactant-Coated Mesoscopic Magnetic Nanoparticles Dispersed Stable Aqueous Magnetic Fluids.

Nanomaterials (Basel) 2021 Nov 9;11(11). Epub 2021 Nov 9.

School of Engineering, RMIT University, Melbourne, VIC 3001, Australia.

The present work reports the synthesis of a stable aqueous magnetic fluid (AMF) by dispersing double-surfactant-coated FeO magnetic nanoparticles (MNPs) in water using a facile ambient scalable wet chemical route. MNPs do not disperse well in water, resulting in low stability. This was improved by dispersing double-surfactant (oleic acid and sodium oleate)-coated MNPs in water, where cross-linking between the surfactants improves the stability of the AMFs. The stability was probed by rheological measurements and all the AMF samples showed a good long-term stability and stability against a gradient magnetic field. Further, the microwave spin resonance behavior of AMFs was studied in detail by corroborating the experimental results obtained from the ferromagnetic resonance (FMR) technique to theoretical predictions by appropriate fittings. A broad spectrum was perceived for AMFs which indicates strong ferromagnetic characteristics. The resonance field shifted to higher magnetic field values with the decrease in particle size as larger-size MNPs magnetize and demagnetize more easily since their magnetic spins can align in the field direction more definitely. The FMR spectra was fitted to obtain various spin resonance parameters. The asymmetric shapes of the FMR spectra were observed with a decrease in particle sizes, which indicates an increase in relaxation time. The relaxation time increased with a decrease in particle sizes (sample A to D) from 37.2779 ps to 42.8301 ps. Further, a detailed investigation of the structural, morphological, and dc magnetic properties of the AMF samples was performed. Room temperature dc magnetic measurements confirmed the superparamagnetic (SPM) characteristics of the AMF and the - plot for each sample was fitted with a Langevin function to obtain the domain magnetization, permeability, and hydrodynamic diameter of the MNPs. The saturation magnetization and coercivity of the AMF samples increased with the increase in dispersed MNPs' size of the samples. The improvement in the stability and magnetic characteristics makes AMFs suitable candidates for various biomedical applications such as drug delivery, magnetic fluid hyperthermia, and biomedicines.
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http://dx.doi.org/10.3390/nano11113009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620981PMC
November 2021

SARS-CoV-2 Sequence Analysis during COVID-19 Case Surge, Liberia, 2021.

Emerg Infect Dis 2021 12 28;27(12):3185-3188. Epub 2021 Oct 28.

In June 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases surged in Liberia. SARS-CoV-2 sequences from patients hospitalized during March-July 2021 revealed the Delta variant was in Liberia in early March and was dominant in June, irrespective of geography. Mutations and deletions suggest multiple SARS-CoV-2 Delta variant introductions.
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http://dx.doi.org/10.3201/eid2712.211818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632187PMC
December 2021

Development of a capture sequencing assay for enhanced detection and genotyping of tick-borne pathogens.

Sci Rep 2021 06 11;11(1):12384. Epub 2021 Jun 11.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.

Inadequate sensitivity has been the primary limitation for implementing high-throughput sequencing for studies of tick-borne agents. Here we describe the development of TBDCapSeq, a sequencing assay that uses hybridization capture probes that cover the complete genomes of the eleven most common tick-borne agents found in the United States. The probes are used for solution-based capture and enrichment of pathogen nucleic acid followed by high-throughput sequencing. We evaluated the performance of TBDCapSeq to surveil samples that included human whole blood, mouse tissues, and field-collected ticks. For Borrelia burgdorferi and Babesia microti, the sensitivity of TBDCapSeq was comparable and occasionally exceeded the performance of agent-specific quantitative PCR and resulted in 25 to > 10,000-fold increase in pathogen reads when compared to standard unbiased sequencing. TBDCapSeq also enabled genome analyses directly within vertebrate and tick hosts. The implementation of TBDCapSeq could have major impact in studies of tick-borne pathogens by improving detection and facilitating genomic research that was previously unachievable with standard sequencing approaches.
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http://dx.doi.org/10.1038/s41598-021-91956-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196166PMC
June 2021

Novel quaranjavirus and other viral sequences identified from ticks parasitizing hunted wildlife in Trinidad and Tobago.

Ticks Tick Borne Dis 2021 07 21;12(4):101730. Epub 2021 Apr 21.

School of Veterinary Medicine, The University of the West Indies, St. Augustine, Trinidad and Tobago.

Hunters are at a higher risk for exposure to zoonotic pathogens due to their close interactions with wildlife and arthropod vectors. In this study, high throughput sequencing was used to explore the viromes of two tick species, Amblyomma dissimile and Haemaphysalis juxtakochi, removed from hunted wildlife in Trinidad and Tobago. We identified sequences from 3 new viral species, from the viral families Orthomyxoviridae, Chuviridae and Tetraviridae in A. dissimile.
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http://dx.doi.org/10.1016/j.ttbdis.2021.101730DOI Listing
July 2021

A metagenomic examination of the pathobiome of the invasive tick species, Haemaphysalis longicornis, collected from a New York City borough, USA.

Ticks Tick Borne Dis 2020 11 22;11(6):101516. Epub 2020 Aug 22.

Columbia University, Center for Infection and Immunity, Mailman School of Public Health, 722 West 168th Street, New York, NY 10032, United States; Columbia University, Department of Epidemiology, Mailman School of Public Health, 722 West 168th Street, New York, NY 10032, United States.

Haemaphysalis longicornis, the Asian longhorned tick, is an invasive tick species that has spread rapidly across the northeastern and southeastern regions of the United States in recent years. This invasive pest species, known to transmit several tick-borne pathogens in its native range, is a potential threat to wildlife, livestock, domestic animals, and humans. Questing larval (n = 25), nymph (n = 10), and adult (n = 123), along with host-derived adult (n = 25) H. longicornis ticks were collected from various locations on Staten Island, NY. The pathobiome of each specimen was examined using two different high throughput sequencing approaches, virus enrichment and shotgun metagenomics. An average of 45,828,061 total reads per sample were recovered from the virus enriched samples and an average of 11,381,144 total reads per sample were obtained using shotgun metagenomics. Aside from endogenous viral sequences, no viruses were identified through either approach. Through shotgun metagenomics, Coxiella-like bacteria, Legionella, Sphingomonas, and other bacterial species were recovered. The Coxiella-like agent was ubiquitous and present at high abundances in all samples, suggesting it may be an endosymbiont. The other bacterial agents are not known to be transmitted by ticks. From these analyses, H. longicornis do not appear to host any endemic human tick-borne pathogens in the New York City region.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101516DOI Listing
November 2020

The Diversity and Distribution of Viruses Associated with Mosquitoes from the Kimberley Region of Western Australia.

Viruses 2020 07 2;12(7). Epub 2020 Jul 2.

Center for Infection and Immunity, Mailman School of Public Health of Columbia University, New York, NY 10034, USA.

Metagenomics revealed an impressive breadth of previously unrecognized viruses. Here, we report the virome of the Skuse mosquito, an important vector of pathogenic arboviruses in Australia. Mosquitoes were collected from three sites in the Kimberley region of Western Australia. Unbiased high-throughput sequencing (HTS) revealed the presence of 16 novel viral sequences that share less than 90% identity with known viruses. None were closely related to pathogenic arboviruses. Viruses were distributed unevenly across sites, indicating a heterogeneous virome. Polymerase chain reaction assays confirmed HTS data and identified marked variation between the virus prevalence identified at each site.
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http://dx.doi.org/10.3390/v12070717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411826PMC
July 2020

Virome Sequencing in Patients With Myocarditis.

Circ Heart Fail 2020 07 26;13(7):e007103. Epub 2020 Jun 26.

Royal Brompton and Harefield Hospitals and Imperial College, London, United Kingdom (T.F.L.).

Background: Polymerase chain reaction analyses of cardiac tissues have detected viral sequences in up to 67% of cases of myocarditis. However, viruses have not been implicated in giant cell myocarditis (GCM). Furthermore, efforts to detect viruses implicated in myocarditis have been unsuccessful in more accessible samples such as peripheral blood.

Methods: We used Virome Capture Sequencing for Vertbrate Viruses (VirCapSeq-VERT), a method that simultaneously screens for all known vertebrate viruses, to investigate viruses in 33 patients with myocarditis. We investigated peripheral blood mononuclear cells (n=24), plasma (n=27), endomyocardial biopsies (n=2), and cardiac tissue samples from explanted hearts (n=13).

Results: Nine patients (27%) had GCM and 4 patients (13%) had fulminant myocarditis. We found the following viruses in the blood of patients with myocarditis: Epstein Barr virus (n=11, 41%), human pegivirus (n=1, 4%), human endogenous retrovirus K (n=27, 100%), and anellovirus (n=15, 56%). All tissue samples from fulminant myocarditis (n=2) and GCM (n=13) contained human endogenous retrovirus K.

Conclusions: No nucleic acids from viruses previously implicated in myocarditis or other human illnesses were detected in relevant amounts in cardiac tissue samples from GCM or in blood samples from other types of myocarditis. These findings do not exclude a role for viral infection in GCM but do suggest that if viruses are implicated, the mechanism is likely to be indirect rather than due to cytotoxic infection of myocardium.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007103DOI Listing
July 2020

Neurologic manifestations in an infant with COVID-19.

Neurology 2020 06 23;94(24):1100-1102. Epub 2020 Apr 23.

From the Department of Neurology (R.D., K.C.C.-M., K.T.T., D.K.M., J.M.B.), Columbia University Irving Medical Center; Center for Infection and Immunity (J.A.G., L.V.C., S.H.W., T.B., K.J., W.I.L., N.M.), Mailman School of Public Health, Columbia University; Department of Epidemiology (W.I.L., N.M.), Mailman School of Public Health, Columbia University; Department of Pediatric Infectious Disease (M.F.), Columbia University Irving Medical Center; and New York Presbyterian Hospital (R.D., K.C.C.-M., K.T.T., M.F., D.K.M., J.M.B.), Columbia University Medical Center, New York, NY.

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http://dx.doi.org/10.1212/WNL.0000000000009653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455334PMC
June 2020

Discovery of Jogalong virus, a novel hepacivirus identified in a Culex annulirostris (Skuse) mosquito from the Kimberley region of Western Australia.

PLoS One 2020 3;15(1):e0227114. Epub 2020 Jan 3.

Center for Infection and Immunity, Mailman School of Public Health of Columbia University, New York, New York, United States of America.

The discovery of hepaciviruses in non-human hosts has accelerated following the advancement of high-throughput sequencing technology. Hepaciviruses have now been described in reptiles, fish, birds, and an extensive array of mammals. Using metagenomic sequencing on pooled samples of field-collected Culex annulirostris mosquitoes, we discovered a divergent hepacivirus-like sequence, named Jogalong virus, from the Kimberley region in northern Western Australia. Using PCR, we screened the same 300 individual mosquitoes and found just a single positive sample (1/300, 0.33%). Phylogenetic analysis of the hepacivirus NS5B protein places Jogalong virus within the genus Hepacivirus but on a distinct and deeply rooted monophyletic branch shared with duck hepacivirus, suggesting a notably different evolutionary history. Vertebrate barcoding PCR targeting two mitochondrial genes, cytochrome c oxidase subunit I and cytochrome b, indicated that the Jogalong virus-positive mosquito had recently fed on the tawny frogmouth (Podargus strigoides), although it is currently unknown whether this bird species contributes to the natural ecology of this virus.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227114PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941808PMC
April 2020

Higher frequency of vertebrate-infecting viruses in the gut of infants born to mothers with type 1 diabetes.

Pediatr Diabetes 2020 03 7;21(2):271-279. Epub 2020 Jan 7.

School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.

Background: Microbial exposures in utero and early life shape the infant microbiome, which can profoundly impact on health. Compared to the bacterial microbiome, very little is known about the virome. We set out to characterize longitudinal changes in the gut virome of healthy infants born to mothers with or without type 1 diabetes using comprehensive virome capture sequencing.

Methods: Healthy infants were selected from Environmental Determinants of Islet Autoimmunity (ENDIA), a prospective cohort of Australian children with a first-degree relative with type 1 diabetes, followed from pregnancy. Fecal specimens were collected three-monthly in the first year of life.

Results: Among 25 infants (44% born to mothers with type 1 diabetes) at least one virus was detected in 65% (65/100) of samples and 96% (24/25) of infants during the first year of life. In total, 26 genera of viruses were identified and >150 viruses were differentially abundant between the gut of infants with a mother with type 1 diabetes vs without. Positivity for any virus was associated with maternal type 1 diabetes and older infant age. Enterovirus was associated with older infant age and maternal smoking.

Conclusions: We demonstrate a distinct gut virome profile in infants of mothers with type 1 diabetes, which may influence health outcomes later in life. Higher prevalence and greater number of viruses observed compared to previous studies suggests significant underrepresentation in existing virome datasets, arising most likely from less sensitive techniques used in data acquisition.
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http://dx.doi.org/10.1111/pedi.12952DOI Listing
March 2020

Discovery of two highly divergent negative-sense RNA viruses associated with the parasitic nematode, , in wild from New York City.

J Gen Virol 2019 10 12;100(10):1350-1362. Epub 2019 Sep 12.

Center for Infection and Immunity, Columbia University, New York, NY, USA.

Recent advances in high-throughput sequencing technology have led to a rapid expansion in the number of viral sequences associated with samples from vertebrates, invertebrates and environmental samples. Accurate host identification can be difficult in assays of complex samples that contain more than one potential host. Using unbiased metagenomic sequencing, we investigated wild house mice () and brown rats () from New York City to determine the aetiology of liver disease. Light microscopy was used to characterize liver disease, and fluorescent microscopy with hybridization was employed to identify viral cell tropism. Sequences representing two novel negative-sense RNA viruses were identified in homogenates of wild house mouse liver tissue: Amsterdam virus and Fulton virus. hybridization localized viral RNA to a parasitic nematode that had infected the mouse liver. RNA from either virus was found within nematode adults and unembryonated eggs. Expanded PCR screening identified brown rats as a second rodent host for as well as both nematode-associated viruses. Our findings indicate that the current diversity of nematode-associated viruses may be underappreciated and that anatomical imaging offers an alternative to computational host assignment approaches.
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http://dx.doi.org/10.1099/jgv.0.001315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363305PMC
October 2019

Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis.

mBio 2019 08 13;10(4). Epub 2019 Aug 13.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) ( = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; = 0.139, 0.002, and 0.009, respectively). The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.
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http://dx.doi.org/10.1128/mBio.01903-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692520PMC
August 2019

Viral Diversity of Tick Species Parasitizing Cattle and Dogs in Trinidad and Tobago.

Sci Rep 2019 07 18;9(1):10421. Epub 2019 Jul 18.

School of Veterinary Medicine, The University of the West Indies, St. Augustine, Trinidad and Tobago.

Ticks are vectors of a wide variety of pathogens that are implicated in mild to severe disease in humans and other animals. Nonetheless, the full range of tick-borne pathogens is unknown. Viruses, in particular, have been neglected in discovery efforts targeting tick-borne agents. High throughput sequencing was used to characterize the virome of 638 ticks, including Rhipicephalus microplus (n = 320), Rhipicephalus sanguineus (n = 300), and Amblyomma ovale (n = 18) collected throughout Trinidad and Tobago in 2017 and 2018. Sequences representing nine viruses were identified, including five novel species within Tymovirales, Bunyavirales, Chuviridae, Rhabdoviridae, and Flaviviridae. Thereafter the frequency of detection of viral sequences in individual tick species was investigated.
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http://dx.doi.org/10.1038/s41598-019-46914-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639388PMC
July 2019

Microbiome analysis of Ixodes scapularis ticks from New York and Connecticut.

Ticks Tick Borne Dis 2019 06 15;10(4):894-900. Epub 2019 Apr 15.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, NY, United States.

We employed high throughput sequencing to survey the microbiomes of Ixodes scapularis collected in New York and Connecticut. We examined 197 individual I. scapularis adults and pools from 132 adults and 197 nymphs. We detected Borrelia burgdorferi sensu stricto in 56.3% of individual ticks, Anaplasma phagocytophilum in 10.6%, Borrelia miyamotoi in 5%, Babesia microti in 7.6%, and Powassan virus in 3.6%. We did not detect Borrelia mayonii, Ehrlichia muris eauclairensis, Bartonella spp. or pathogenic Babesia species other than B. microti. The most abundant bacterium (65%), and only rickettsial species identified, was the endosymbiont Rickettsia buchneri. A filarial nematode was found in 13.7% of adult ticks. Fourteen viruses were detected including South Bay virus (22%) and blacklegged tick phlebovirus 1 and 2 (73%). This study provides insight into the microbial diversity of I. scapularis in New York State and Connecticut.
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http://dx.doi.org/10.1016/j.ttbdis.2019.04.011DOI Listing
June 2019

A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia.

PLoS One 2019 10;14(4):e0214227. Epub 2019 Apr 10.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, United States of America.

Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214227PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457491PMC
December 2019

A Novel Orthohepadnavirus Identified in a Dead Maxwell's Duiker () in Taï National Park, Côte d'Ivoire.

Viruses 2019 03 19;11(3). Epub 2019 Mar 19.

Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, 13353 Berlin, Germany.

New technologies enable viral discovery in a diversity of hosts, providing insights into viral evolution. We used one such approach, the virome capture sequencing for vertebrate viruses (VirCapSeq-VERT) platform, on 21 samples originating from six dead Maxwell's duikers () from Taï National Park, Côte d'Ivoire. We detected the presence of an orthohepadnavirus in one animal and characterized its 3128 bp genome. The highest viral copy numbers were detected in the spleen, followed by the lung, blood, and liver, with the lowest copy numbers in the kidney and heart; the virus was not detected in the jejunum. Viral copy numbers in the blood were in the range known from humans with active chronic infections leading to liver histolytic damage, suggesting this virus could be pathogenic in duikers, though many orthohepadnaviruses appear to be apathogenic in other hosts, precluding a formal test of this hypothesis. The virus was not detected in 29 other dead duiker samples from the Côte d'Ivoire and Central African Republic, suggesting either a spillover event or a low prevalence in these populations. Phylogenetic analysis placed the virus as a divergent member of the mammalian clade of orthohepadnaviruses, though its relationship to other orthohepadnaviruses remains uncertain. This represents the first orthohepadnavirus described in an artiodactyl. We have tentatively named this new member of the genus (family ), Taï Forest hepadnavirus. Further studies are needed to determine whether it, or some close relatives, are present in a broader range of artiodactyls, including livestock.
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http://dx.doi.org/10.3390/v11030279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466360PMC
March 2019

DEvis: an R package for aggregation and visualization of differential expression data.

BMC Bioinformatics 2019 Mar 4;20(1):110. Epub 2019 Mar 4.

Center for Infection and Immunity, Mailman School of Public Health of Columbia University, 722 West 168th St., New York, NY, 10032, USA.

Background: Existing tools for the aggregation and visualization of differential expression data have discrete functionality and require that end-users rely on multiple software packages with complex dependencies or manually manipulate data for analysis and interpretation. Furthermore, at present, data aggregation and visualization are laborious, time consuming, and subject to human error. This is a serious limitation on the current state of differential transcriptomic analysis, which makes it necessary to expend extensive time and resources to reach the point where biological meaning can be interpreted. Such an approach for analysis also leads to scattered and non-standardized code, unsystematic project management and non-reproducible result sets.

Results: Here, we present a differential expression analysis toolkit, DEvis, that provides a powerful, integrated solution for the analysis of differential expression data with a rapid turnaround time. DEvis has simple installation requirements and provides a convenient, user-friendly R package that addresses the issues inherent to complex multi-factor experiments, such as multiple contrast aggregation and integration, result sorting and selection, visualization, project management, and reproducibility. This tool increases the capabilities of differential expression analysis while reducing workload and the potential for manual error. Furthermore, it provides a much-needed encapsulation of scattered functionality, making large and complex analysis more efficient and reproducible.

Conclusion: DEvis provides a wide range of powerful visualization, data aggregation, and project management tools that provide flexibility and speed in analysis. The functionality provided by DEVis increases efficiency of analysis and supplies researchers with new and relevant means for the analysis of large and complicated transcriptomic experiments. DEvis furthermore incorporates automatic project management capabilities, which standardizes analysis and ensures the reproducibility of results. After the establishment of statistical frameworks that identify differentially expressed genes, this package is the next logical step for differential transcriptomic analysis, establishing the critical framework necessary to manipulate, explore, and extract biologically relevant meaning from differential expression data.
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http://dx.doi.org/10.1186/s12859-019-2702-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399874PMC
March 2019

Distinct Gut Virome Profile of Pregnant Women With Type 1 Diabetes in the ENDIA Study.

Open Forum Infect Dis 2019 Feb 16;6(2):ofz025. Epub 2019 Jan 16.

School of Women's and Children's Health, University of New South Wales, Sydney, Australia.

Background: The importance of gut bacteria in human physiology, immune regulation, and disease pathogenesis is well established. In contrast, the composition and dynamics of the gut virome are largely unknown; particularly lacking are studies in pregnancy. We used comprehensive virome capture sequencing to characterize the gut virome of pregnant women with and without type 1 diabetes (T1D), longitudinally followed in the Environmental Determinants of Islet Autoimmunity study.

Methods: In total, 61 pregnant women (35 with T1D and 26 without) from Australia were examined. Nucleic acid was extracted from serial fecal specimens obtained at prenatal visits, and viral genomes were sequenced by virome capture enrichment. The frequency, richness, and abundance of viruses were compared between women with and without T1D.

Results: Two viruses were more prevalent in pregnant women with T1D: picobirnaviruses (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.0-17.1; = .046) and tobamoviruses (OR, 3.2; 95% CI, 1.1-9.3; = .037). The abundance of 77 viruses significantly differed between the 2 maternal groups (≥2-fold difference; < .02), including 8 types present at a higher abundance in women with T1D.

Conclusions: These findings provide novel insight into the composition of the gut virome during pregnancy and demonstrate a distinct profile of viruses in women with T1D.
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http://dx.doi.org/10.1093/ofid/ofz025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386807PMC
February 2019

Emergence of the East-Central-South-African genotype of Chikungunya virus in Brazil and the city of Rio de Janeiro may have occurred years before surveillance detection.

Sci Rep 2019 02 26;9(1):2760. Epub 2019 Feb 26.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA.

Brazil, which is hyperendemic for dengue virus (DENV), has had recent Zika (ZIKV) and (CHIKV) Chikungunya virus outbreaks. Since March 2016, CHIKV is the arbovirus infection most frequently diagnosed in Rio de Janeiro. In the analysis of 1835 syndromic patients, screened by real time RT-PCR, 56.4% of the cases were attributed to CHIKV, 29.6% to ZIKV, and 14.1% to DENV-4. Sequence analyses of CHIKV from sixteen samples revealed that the East-Central-South-African (ECSA) genotype of CHIKV has been circulating in Brazil since 2013 [95% bayesian credible interval (BCI): 03/2012-10/2013], almost a year before it was detected by arbovirus surveillance program. Brazilian cases are related to Central African Republic sequences from 1980's. To the best of our knowledge, given the available sequence published here and elsewhere, the ECSA genotype was likely introduced to Rio de Janeiro early on 2014 (02/2014; BCI: 07/2013-08/2014) through a single event, after primary circulation in the Bahia state at the Northestern Brazil in the previous year. The observation that the ECSA genotype of CHIKV was circulating undetected underscores the need for improvements in molecular methods for viral surveillance.
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http://dx.doi.org/10.1038/s41598-019-39406-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391440PMC
February 2019

Higher abundance of enterovirus A species in the gut of children with islet autoimmunity.

Sci Rep 2019 02 11;9(1):1749. Epub 2019 Feb 11.

School of Women's and Children's Health, University of New South Wales Faculty of Medicine, Sydney, Australia.

Enteroviruses (EVs) are prime candidate environmental triggers of islet autoimmunity (IA), with potential as vaccine targets for type 1 diabetes prevention. However, the use of targeted virus detection methods and the selective focus on EVs by most studies increases the risk for substantial investigation bias and an overestimated association between EV and type 1 diabetes. Here we performed comprehensive virome-capture sequencing to examine all known vertebrate-infecting viruses without bias in 182 specimens (faeces and plasma) collected before or at seroconversion from 45 case children with IA and 48 matched controls. From >2.6 billion reads, 28 genera of viruses were detected and 62% of children (58/93) were positive for ≥1 vertebrate-infecting virus. We identified 129 viruses as differentially abundant between the gut of cases and controls, including 5 EV-A types significantly more abundant in the cases. Our findings further support EV's hypothesised contribution to IA and corroborate the proposal that viral load may be an important parameter in disease pathogenesis. Furthermore, our data indicate a previously unrecognised association of IA with higher EV-A abundance in the gut of children and provide a catalog of viruses to be interrogated further to determine a causal link between virus infection and type 1 diabetes.
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http://dx.doi.org/10.1038/s41598-018-38368-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370883PMC
February 2019

Investigation of the Plasma Virome from Cases of Unexplained Febrile Illness in Tanzania from 2013 to 2014: a Comparative Analysis between Unbiased and VirCapSeq-VERT High-Throughput Sequencing Approaches.

mSphere 2018 08 22;3(4). Epub 2018 Aug 22.

Center for Infection & Immunity, Columbia University, New York, New York, USA

High-throughput sequencing can provide insights into epidemiology and medicine through comprehensive surveys of viral genetic sequences in environmental and clinical samples. Here, we characterize the plasma virome of Tanzanian patients with unexplained febrile illness by using two high-throughput sequencing methods: unbiased sequencing and VirCapSeq-VERT (a positive selection system). Sequences from dengue virus 2, West Nile virus, human immunodeficiency virus type 1, human pegivirus, and Epstein-Barr virus were identified in plasma. Both sequencing strategies recovered nearly complete genomes in samples containing multiple viruses. Whereas VirCapSeq-VERT had better sensitivity, unbiased sequencing provided better coverage of genome termini. Together, these data demonstrate the utility of high-throughput sequencing strategies in outbreak investigations. Characterization of the viruses found in the blood of febrile patients provides information pertinent to public health and diagnostic medicine. PCR and culture have historically played an important role in clinical microbiology; however, these methods require a targeted approach and may lack the capacity to identify novel or mixed viral infections. High-throughput sequencing can overcome these constraints. As the cost of running multiple samples continues to decrease, the implementation of high-throughput sequencing for diagnostic purposes is becoming more feasible. Here we present a comparative analysis of findings from an investigation of unexplained febrile illness using two strategies: unbiased high-throughput sequencing and VirCapSeq-VERT, a positive selection high-throughput sequencing system.
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http://dx.doi.org/10.1128/mSphere.00311-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106054PMC
August 2018

Viral Diversity of House Mice in New York City.

mBio 2018 04 17;9(2). Epub 2018 Apr 17.

Center for Infection and Immunity, Columbia University, New York, New York, USA

The microbiome of wild (house mouse), a globally distributed invasive pest that resides in close contact with humans in urban centers, is largely unexplored. Here, we report analysis of the fecal virome of house mice in residential buildings in New York City, NY. Mice were collected at seven sites in Manhattan, Queens, Brooklyn, and the Bronx over a period of 1 year. Unbiased high-throughput sequencing of feces revealed 36 viruses from 18 families and 21 genera, including at least 6 novel viruses and 3 novel genera. A representative screen of 15 viruses by PCR confirmed the presence of 13 of these viruses in liver. We identified an uneven distribution of diversity, with several viruses being associated with specific locations. Higher mouse weight was associated with an increase in the number of viruses detected per mouse, after adjusting for site, sex, and length. We found neither genetic footprints to known human viral pathogens nor antibodies to lymphocytic choriomeningitis virus. Mice carry a wide range of infectious agents with zoonotic potential. Their proximity to humans in the built environment is therefore a concern for public health. Laboratory mice are also the most common experimental model for investigating the pathobiology of infectious diseases. In this survey of mice trapped in multiple locations within New York City over a period of 1 year, we found a diverse collection of viruses that includes some previously not associated with house mice and others that appear to be novel. Although we found no known human pathogens, our findings provide insights into viral ecology and may yield models that have utility for clinical microbiology.
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http://dx.doi.org/10.1128/mBio.01354-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904411PMC
April 2018

Identification of Novel Viruses in , , and Ticks.

mSphere 2018 Mar-Apr;3(2). Epub 2018 Mar 7.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA.

Ticks carry a wide range of known human and animal pathogens and are postulated to carry others with the potential to cause disease. Here we report a discovery effort wherein unbiased high-throughput sequencing was used to characterize the virome of 2,021 ticks, including ( 1,138), ( 720), and ( 163), collected in New York, Connecticut, and Virginia in 2015 and 2016. We identified 33 viruses, including 24 putative novel viral species. The most frequently detected viruses were phylogenetically related to members of the and families, as well as the recently proposed . Our work expands our understanding of tick viromes and underscores the high viral diversity that is present in ticks. The incidence of tick-borne disease is increasing, driven by rapid geographical expansion of ticks and the discovery of new tick-associated pathogens. The examination of the tick microbiome is essential in order to understand the relationship between microbes and their tick hosts and to facilitate the identification of new tick-borne pathogens. Genomic analyses using unbiased high-throughput sequencing platforms have proven valuable for investigations of tick bacterial diversity, but the examination of tick viromes has historically not been well explored. By performing a comprehensive virome analysis of the three primary tick species associated with human disease in the United States, we gained substantial insight into tick virome diversity and can begin to assess a potential role of these viruses in the tick life cycle.
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http://dx.doi.org/10.1128/mSphere.00614-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853492PMC
March 2018

Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay.

mBio 2018 03 6;9(2). Epub 2018 Mar 6.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA

Zika virus (ZIKV) is implicated in fetal stillbirth, microcephaly, intracranial calcifications, and ocular anomalies following vertical transmission from infected mothers. In adults, infection may trigger autoimmune inflammatory polyneuropathy. Transmission most commonly follows the bite of infected mosquitoes but may also occur through sexual intercourse or receipt of blood products. Definitive diagnosis through detection of viral RNA is possible in serum or plasma within 10 days of disease onset, in whole blood within 3 weeks of onset, and in semen for up to 3 months. Serological diagnosis is nonetheless critical because few patients have access to molecular diagnostics during the acute phase of infection and infection may be associated with only mild or inapparent disease that does not prompt molecular testing. Serological diagnosis is confounded by cross-reactivity of immune sera with other flaviviruses endemic in the areas where ZIKV has recently emerged. Accordingly, we built a high-density microarray comprising nonredundant 12-mer peptides that tile, with one-residue overlap, the proteomes of Zika, dengue, yellow fever, West Nile, Ilheus, Oropouche, and chikungunya viruses. Serological analysis enabled discovery of a ZIKV NS2B 20-residue peptide that had high sensitivity (96.0%) and specificity (95.9%) versus natural infection with or vaccination against dengue, chikungunya, yellow fever, West Nile, tick-borne encephalitis, or Japanese encephalitis virus in a microarray assay and an enzyme-linked immunosorbent assay (ELISA) of early-convalescent-phase sera (2 to 3 weeks after onset of symptomatic infection). The emergence of Zika virus (ZIKV) as a teratogen is a profound challenge to global public health. Molecular diagnosis of infection is straightforward during the 3-week period when patients are viremic. However, serological diagnosis thereafter of historical exposure has been confounded by cross-reactivity. Using high-density peptide arrays that tile the proteomes of a selection of flaviviruses to identify a ZIKV-specific peptide, we established two assays that enable sensitive and specific diagnosis of exposure to ZIKV. These assays may be useful in guiding clinical management of mothers at risk for potential exposure to ZIKV and enable insights into the epidemiology of ZIKV infections.
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http://dx.doi.org/10.1128/mBio.00095-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844993PMC
March 2018

Dipolar Interaction and Magneto-Viscoelasticity in Nanomagnetic Fluid.

J Nanosci Nanotechnol 2018 Apr;18(4):2746-2751

CSIR-National Physical Laboratory, Dr. K.S. Krishna Road, New Delhi 110012, India; Academy of Scientific and Innovative Research-NPL Campus, New Delhi 110012, India.

We investigate the effect of dilution on dipolar interaction with linear and non-linear rheological properties of kerosene based magnetic fluid. The steady-state behavior demonstrate a shear thinning behavior and corroborated with a power law, (η = c γ ˙ n + η∞) exponent, n ≤ 1. The shear-induced-breakup (separation) of nanoparticles and the yielding behavior has been explained by Bingham model. Moreover, the magnetoviscous effect showed an initial increase at low shear rate and decrease at higher shear rate. Further, specific viscosity (ηF)-versus-Mason number (Mn) shows a perfect scaling at lower Mn (≤10-4) confirming negligible thermal and colloidal forces. Whereas, at higher Mn (≥10-3) deviation from collapse indicates the dominance of Brownian forces acting on nanofluids. The magnetic field dependent elastic (G') and viscous (G″) modulus reveal a crossover from viscoelastic-to-viscous behavior of nanofluid at critical concentration. Finally, we compare viscoelastic results with De Gans diagonal scaling theory to correlate the functional dependence of storage and loss modules with different particle volume concentration.
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http://dx.doi.org/10.1166/jnn.2018.14532DOI Listing
April 2018

Highly Sensitive Virome Capture Sequencing Technique VirCapSeq-VERT Identifies Partial Noncoding Sequences but no Active Viral Infection in Cutaneous T-Cell Lymphoma.

J Invest Dermatol 2018 07 7;138(7):1671-1673. Epub 2018 Feb 7.

Department of Dermatology, Columbia University Medical Center, New York, New York, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2018.01.024DOI Listing
July 2018

New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product.

Emerg Infect Dis 2018 02;24(2):303-310

Equine serum hepatitis (i.e., Theiler's disease) is a serious and often life-threatening disease of unknown etiology that affects horses. A horse in Nebraska, USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus antitoxin. We identified an unknown parvovirus in serum and liver of the dead horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H) shares <50% protein identity with its phylogenetic relatives of the genus Copiparvovirus. Next, we experimentally infected 2 horses using a tetanus antitoxin contaminated with EqPV-H. Viremia developed, the horses seroconverted, and acute hepatitis developed that was confirmed by clinical, biochemical, and histopathologic testing. We also determined that EqPV-H is an endemic infection because, in a cohort of 100 clinically normal adult horses, 13 were viremic and 15 were seropositive. We identified a new virus associated with equine serum hepatitis and confirmed its pathogenicity and transmissibility through contaminated biological products.
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http://dx.doi.org/10.3201/eid2402.171031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782890PMC
February 2018
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