Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-13 (of 13 Records) |
Query Trace: Whitmer SLM[original query] |
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Completed genome segments of Maciel, Lechiguanas, and Laguna Negra orthohantaviruses
Shedroff E , Whitmer SLM , Mobley M , Morales-Betoulle M , Martin ML , Brignone J , Sen C , Nazar Y , Montgomery JM , Klena JD . Microbiol Resour Announc 2024 e0044124 ![]() ![]() New World orthohantaviruses are rodent-borne tri-segmented viruses that cause hantavirus cardiopulmonary syndrome in humans in the Americas. Molecular diagnostics for orthohantaviruses can be improved with more sequence data. Reported here are completed genomes for Lechiguanas, Maciel, and Laguna Negra viruses. |
Human Orthohantavirus disease prevalence and genotype distribution in the U.S., 2008–2020: a retrospective observational study
Whitmer SLM , Whitesell A , Mobley M , Talundzic E , Shedroff E , Cossaboom CM , Messenger S , Deldari M , Bhatnagar J , Estetter L , Zufan S , Cannon D , Chiang CF , Gibbons A , Krapiunaya I , Morales-Betoulle M , Choi M , Knust B , Amman B , Montgomery JM , Shoemaker T , Klena JD . Lancet Reg Health - Am 2024 37 ![]() ![]() Background: In the United States (U.S.), hantavirus pulmonary syndrome (HPS) and non-HPS hantavirus infection are nationally notifiable diseases. Criteria for identifying human cases are based on clinical symptoms (HPS or non-HPS) and acute diagnostic results (IgM+, rising IgG+ titers, RT-PCR+, or immunohistochemistry (IHC)+). Here we provide an overview of diagnostic testing and summarize human Hantavirus disease occurrence and genotype distribution in the U.S. from 2008 to 2020. Methods: Epidemiological data from the national hantavirus registry was merged with laboratory diagnostic testing results performed at the CDC. Residual hantavirus-positive specimens were sequenced, and the available epidemiological and genetic data sets were linked to conduct a genomic epidemiological study of hantavirus disease in the U.S. Findings: From 1993 to 2020, 833 human hantavirus cases have been identified, and from 2008 to 2020, 335 human cases have occurred. Among New World (NW) hantavirus cases detected at the CDC diagnostic laboratory (representing 29.2% of total cases), most (85.0%) were detected during acute disease, however, some convalescent cases were detected in states not traditionally associated with hantavirus infections (Connecticut, Missouri, New Jersey, Pennsylvania, Tennessee, and Vermont). From 1993 to 2020, 94.9% (745/785) of U.S. hantaviruses cases were detected west of the Mississippi with 45.7% (359/785) in the Four Corners region of the U.S. From 2008 to 2020, 67.7% of NW hantavirus cases were detected between the months of March and August. Sequencing of RT-PCR-positive cases demonstrates a geographic separation of Orthohantavirus sinnombreense species [Sin Nombre virus (SNV), New York virus, and Monongahela virus]; however, there is a large gap in viral sequence data from the Northwestern and Central U.S. Finally, these data indicate that commercial IgM assays are not concordant with CDC-developed assays, and that “concordant positive” (i.e., commercial IgM+ and CDC IgM+ results) specimens exhibit clinical characteristics of hantavirus disease. Interpretation: Hantaviral disease is broadly distributed in the contiguous U.S, viral variants are localised to specific geographic regions, and hantaviral disease infrequently detected in most Southeastern states. Discordant results between two diagnostic detection methods highlight the need for an improved standardised testing plan in the U.S. Hantavirus surveillance and detection will continue to improve with clearly defined, systematic reporting methods, as well as explicit guidelines for clinical characterization and diagnostic criteria. Funding: This work was funded by core funds provided to the Viral Special Pathogens Branch at CDC. © 2024 |
Sosuga virus detected in Egyptian rousette bats (Rousettus aegyptiacus) in Sierra Leone
Amman BR , Koroma AH , Schuh AJ , Conteh I , Sealy TK , Foday I , Johnny J , Bakarr IA , Whitmer SLM , Wright EA , Gbakima AA , Graziano J , Bangura C , Kamanda E , Osborne A , Saidu E , Musa JA , Bangura DF , Williams SMT , Fefegula GM , Sumaila C , Jabaty J , James FH , Jambai A , Garnett K , Kamara TF , Towner JS , Lebbie A . Viruses 2024 16 (4) ![]() ![]() Sosuga virus (SOSV), a rare human pathogenic paramyxovirus, was first discovered in 2012 when a person became ill after working in South Sudan and Uganda. During an ecological investigation, several species of bats were sampled and tested for SOSV RNA and only one species, the Egyptian rousette bat (ERBs; Rousettus aegyptiacus), tested positive. Since that time, multiple other species have been sampled and ERBs in Uganda have continued to be the only species of bat positive for SOSV infection. Subsequent studies of ERBs with SOSV demonstrated that ERBs are a competent host for SOSV and shed this infectious virus while exhibiting only minor infection-associated pathology. Following the 2014 Ebola outbreak in West Africa, surveillance efforts focused on discovering reservoirs for zoonotic pathogens resulted in the capture and testing of many bat species. Here, SOSV RNA was detected by qRT-PCR only in ERBs captured in the Moyamba District of Sierra Leone in the central region of the country. These findings represent a substantial range extension from East Africa to West Africa for SOSV, suggesting that this paramyxovirus may occur in ERB populations throughout its sub-Saharan African range. |
Case of human orthohantavirus infection, Michigan, USA, 2021
Goodfellow SM , Nofchissey RA , Arsnoe D , Ye C , Lee S , Park J , Kim WK , Chandran K , Whitmer SLM , Klena JD , Dyal JW , Shoemaker T , Riner D , Stobierski MG , Signs K , Bradfute SB . Emerg Infect Dis 2024 30 (4) 817-821 ![]() ![]() Orthohantaviruses cause hantavirus cardiopulmonary syndrome; most cases occur in the southwest region of the United States. We discuss a clinical case of orthohantavirus infection in a 65-year-old woman in Michigan and the phylogeographic link of partial viral fragments from the patient and rodents captured near the presumed site of infection. |
Novel Oliveros-like Clade C mammarenaviruses from rodents in Argentina, 1990-2020
Shedroff E , Martin ML , Whitmer SLM , Brignone J , Garcia JB , Sen C , Nazar Y , Fabbri C , Morales-Betoulle M , Mendez J , Montgomery J , Morales MA , Klena JD . Viruses 2024 16 (3) ![]() ![]() Following an Argentine Hemorrhagic Fever (AHF) outbreak in the early 1990s, a rodent survey for Junín virus, a New World Clade B arenavirus, in endemic areas of Argentina was conducted. Since 1990, INEVH has been developing eco-epidemiological surveillance of rodents, inside and outside the Argentine Hemorrhagic Fever endemic area. Samples from rodents captured between 1993 and 2019 that were positive for Arenavirus infection underwent Sanger and unbiased, Illumina-based high-throughput sequencing, which yielded 5 complete and 88 partial Mammarenaviruses genomes. Previously, 11 genomes representing four species of New World arenavirus Clade C existed in public records. This work has generated 13 novel genomes, expanding the New World arenavirus Clade C to 24 total genomes. Additionally, two genomes exhibit sufficient genetic diversity to be considered a new species, as per ICTV guidelines (proposed name Mammarenavirus vellosense). The 13 novel genomes exhibited reassortment between the small and large segments in New World Mammarenaviruses. This work demonstrates that Clade C Mammarenavirus infections circulate broadly among Necromys species in the Argentine Hemorrhagic Fever endemic area; however, the risk for Clade C Mammarenavirus human infection is currently unknown. |
HantaNet: A new microbetrace application for hantavirus classification, genomic surveillance, epidemiology and outbreak investigations
Cintron R , Whitmer SLM , Moscoso E , Campbell EM , Kelly R , Talundzic E , Mobley M , Chiu KW , Shedroff E , Shankar A , Montgomery JM , Klena JD , Switzer WM . Viruses 2023 15 (11) ![]() ![]() Hantaviruses zoonotically infect humans worldwide with pathogenic consequences and are mainly spread by rodents that shed aerosolized virus particles in urine and feces. Bioinformatics methods for hantavirus diagnostics, genomic surveillance and epidemiology are currently lacking a comprehensive approach for data sharing, integration, visualization, analytics and reporting. With the possibility of hantavirus cases going undetected and spreading over international borders, a significant reporting delay can miss linked transmission events and impedes timely, targeted public health interventions. To overcome these challenges, we built HantaNet, a standalone visualization engine for hantavirus genomes that facilitates viral surveillance and classification for early outbreak detection and response. HantaNet is powered by MicrobeTrace, a browser-based multitool originally developed at the Centers for Disease Control and Prevention (CDC) to visualize HIV clusters and transmission networks. HantaNet integrates coding gene sequences and standardized metadata from hantavirus reference genomes into three separate gene modules for dashboard visualization of phylogenetic trees, viral strain clusters for classification, epidemiological networks and spatiotemporal analysis. We used 85 hantavirus reference datasets from GenBank to validate HantaNet as a classification and enhanced visualization tool, and as a public repository to download standardized sequence data and metadata for building analytic datasets. HantaNet is a model on how to deploy MicrobeTrace-specific tools to advance pathogen surveillance, epidemiology and public health globally. |
New Lineage of Lassa Virus, Togo, 2016.
Whitmer SLM , Strecker T , Cadar D , Dienes HP , Faber K , Patel K , Brown SM , Davis WG , Klena JD , Rollin PE , Schmidt-Chanasit J , Fichet-Calvet E , Noack B , Emmerich P , Rieger T , Wolff S , Fehling SK , Eickmann M , Mengel JP , Schultze T , Hain T , Ampofo W , Bonney K , Aryeequaye JND , Ribner B , Varkey JB , Mehta AK , Lyon GM 3rd , Kann G , De Leuw P , Schuettfort G , Stephan C , Wieland U , Fries JWU , Kochanek M , Kraft CS , Wolf T , Nichol ST , Becker S , Ströher U , Günther S . Emerg Infect Dis 2018 24 (3) 599-602 ![]() ![]() We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo. |
Inference of Nipah virus evolution, 1999-2015.
Whitmer SLM , Lo MK , Sazzad HMS , Zufan S , Gurley ES , Sultana S , Amman B , Ladner JT , Rahman MZ , Doan S , Satter SM , Flora MS , Montgomery JM , Nichol ST , Spiropoulou CF , Klena JD . Virus Evol 2021 7 (1) veaa062 ![]() ![]() ![]() Despite near-annual human outbreaks of Nipah virus (NiV) disease in Bangladesh, typically due to individual spillover events from the local bat population, only twenty whole-genome NiV sequences exist from humans and ten from bats. NiV whole-genome sequences from annual outbreaks have been challenging to generate, primarily due to the low viral load in human throat swab and serum specimens. Here, we used targeted enrichment with custom NiV-specific probes and generated thirty-five additional unique full-length genomic sequences directly from human specimens and viral isolates. We inferred the temporal and geographic evolutionary history of NiV in Bangladesh and expanded a tool to visualize NiV spatio-temporal spread from a Bayesian continuous diffusion analysis. We observed that strains from Bangladesh segregated into two distinct clades that have intermingled geographically in Bangladesh over time and space. As these clades expanded geographically and temporally, we did not observe evidence for significant branch and site-specific selection, except for a single site in the Henipavirus L polymerase. However, the Bangladesh 1 and 2 clades are differentiated by mutations initially occurring in the polymerase, with additional mutations accumulating in the N, G, F, P, and L genes on external branches. Modeling the historic geographical and temporal spread demonstrates that while widespread, NiV does not exhibit significant genetic variation in Bangladesh. Thus, future public health measures should address whether NiV within in the bat population also exhibits comparable genetic variation, if zoonotic transmission results in a genetic bottleneck and if surveillance techniques are detecting only a subset of NiV. Copyright © 2020 Published by Oxford University Press 2020. This work is written by a US Government employee and is in the public domain in the US. |
Inhibition of Nipah Virus by Defective Interfering Particles.
Welch SR , Tilston NL , Lo MK , Whitmer SLM , Harmon JR , Scholte FEM , Spengler JR , Duprex WP , Nichol ST , Spiropoulou CF . J Infect Dis 2020 221 S460-S470 ![]() ![]() The error-prone nature of ribonucleic acid (RNA)-dependent RNA polymerases drives the diversity of RNA virus populations. Arising within this diversity is a subset of defective viral genomes that retain replication competency, termed defective interfering (DI) genomes. These defects are caused by aberrant viral polymerase reinitiation on the same viral RNA template (deletion DI species) or the nascent RNA strand (copyback DI species). Defective interfering genomes have previously been shown to alter the dynamics of a viral population by interfering with normal virus replication and/or by stimulating the innate immune response. In this study, we investigated the ability of artificially produced DI genomes to inhibit Nipah virus (NiV), a highly pathogenic biosafety level 4 paramyxovirus. High multiplicity of infection passaging of both NiV clinical isolates and recombinant NiV in Vero cells generated an extensive DI population from which individual DIs were identified using next-generation sequencing techniques. Assays were established to generate and purify both naturally occurring and in silico-designed DIs as fully encapsidated, infectious virus-like particles termed defective interfering particles (DIPs). We demonstrate that several of these NiV DIP candidates reduced NiV titers by up to 4 logs in vitro. These data represent a proof-of-principle that a therapeutic application of DIPs to combat NiV infections may be an alternative source of antiviral control for this disease. |
Characterization of Novel Reoviruses [Wad Medani virus (Orbivirus) and Kundal (Coltivirus)] collected from Hyalomma antolicum ticks in India during CCHF surveillance.
Yadav PD , Whitmer SLM , Sarkale P , Ng TFF , Goldsmith CS , Nyayanit DA , Esona MD , Shrivastava-Ranjan P , Lakra R , Pardeshi P , Majumdar TD , Francis A , Klena JD , Nichol ST , Stroher U , Mourya D . J Virol 2019 93 (13) ![]() In 2011, ticks were collected from livestock following an outbreak of Crimean Congo Hemorrhagic fever (CCHF) in Gujarat state, India. CCHF-negative Hyalomma anatolicum tick pools were passaged for virus isolation, and two virus isolates were obtained, designated Karyana virus (KARYV) and Kundal virus (KUNDV) respectively. Traditional RT-PCR identification of known viruses was unsuccessful, but a next-generation sequencing approach identified KARYV and KUNDV as viruses in the Reoviridae family, Orbivirus, and Coltivirus genera, respectively. Viral genomes were de novo assembled, yielding 10 complete segments of KARYV and 12 nearly complete segments of KUNDV. The VP1 gene of KARYV shared a most recent common ancestor with Wad Medani virus (WMV), strain Ar495, and based on nucleotide identity we demonstrate that it is a novel WMV strain. The VP1 segment of KUNDV shares a common ancestor with Colorado tick fever virus, Eyach virus, Tai Forest reovirus and Tarumizu tick virus from the Coltivirus genus. Based on VP1, VP6, VP7, and VP12 nucleotide and amino acid identity, KUNDV is proposed to be a new species of Coltivirus Electron microscopy supported the classification of KARYV and KUNDV as reoviruses and identified replication morphology consistent with other Orbi- and Colti- viruses. The identification of novel tick-borne viruses carried by the CCHF vector is an important step in the characterization of their potential role in human and animal pathogenesis.Importance Ticks, mosquitoes, as well Culicoides, can transmit viruses in the Reoviridae family. With the help of next-generation sequencing (NGS), previously unreported reoviruses such as equine encephalosis virus, Wad Medani virus (WMV), Kammanvanpettai virus (KVPTV) and with this report, KARYV and KUNDV have been discovered and characterized in India. The isolation of KUNDV and KARYV from Hyalomma anatolicum, which is a known vector for zoonotic pathogens, such as Crimean Congo Hemorrhagic Fever virus, Babesia, Theileria and Anaplasma species, identifies arboviruses with the potential to transmit to humans. Characterization of these KUNDV and KARYV isolated from Hyalomma ticks is critical for the development of specific serological and molecular assays that can be used to determine the association of these viruses with disease in humans and livestock. |
Notes from the Field: Contact tracing investigation after first case of Andes virus in the United States - Delaware, February 2018
Kofman A , Eggers P , Kjemtrup A , Hall R , Brown SM , Morales-Betoulle M , Graziano J , Zufan SE , Whitmer SLM , Cannon DL , Chiang CF , Choi MJ , Rollin PE , Cetron MS , Yaglom HD , Duwell M , Kuhar DT , Kretschmer M , Knust B , Klena JD , Alvarado-Ramy F , Shoemaker T , Towner JS , Nichol ST . MMWR Morb Mortal Wkly Rep 2018 67 (41) 1162-1163 In January 2018, a woman admitted to a Delaware hospital tested positive for New World hantavirus immunoglobulin M (IgM) and immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Subsequent testing by CDC’s Viral Special Pathogens Branch detected New World hantavirus by nested reverse transcription–polymerase chain reaction (RT-PCR) and Andes virus by nucleic acid sequencing. This case represents the first confirmed importation of Andes virus infection into the United States; two imported cases have also been reported in Switzerland (1). Before her illness, the patient had traveled to the Andes region of Argentina and Chile from December 20, 2017, to January 3, 2018. She stayed in cabins and youth hostels in reportedly poor condition. No rodent exposures were reported. After returning to the United States on January 10, she developed fever, malaise, and myalgias on January 14. On January 17, while ill, she traveled on two commercial domestic flights. She was hospitalized during January 20–25 in Delaware and discharged to her home after clinical recovery. |
Characterization of Unknown Orthobunya-Like Viruses from India.
Whitmer SLM , Yadav PD , Sarkale P , Chaubal GY , Francis A , Klena J , Nichol ST , Stroher U , Mourya DT . Viruses 2018 10 (9) ![]() ![]() Next-generation sequencing (NGS) of agents causing idiopathic human diseases has been crucial in the identification of novel viruses. This study describes the isolation and characterization of two novel orthobunyaviruses obtained from a jungle myna and a paddy bird from Karnataka State, India. Using an NGS approach, these isolates were classified as Cat Que and Balagodu viruses belonging to the Manzanilla clade of the Simbu serogroup. Closely related viruses in the Manzanilla clade have been isolated from mosquitos, humans, birds, and pigs across a wide geographic region. Since Orthobunyaviruses exhibit high reassortment frequency and can cause acute, self-limiting febrile illness, these data suggest that human and livestock infections of the Oya/Cat Que/Manzanilla virus may be more widespread and/or under-reported than anticipated. It therefore becomes imperative to identify novel and unknown viruses in order to understand their role in human and animal pathogenesis. The current study is a step forward in this regard and would act as a prototype method for isolation, identification and detection of several other emerging viruses. |
Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors.
Whitmer SLM , Ladner JT , Wiley MR , Patel K , Dudas G , Rambaut A , Sahr F , Prieto K , Shepard SS , Carmody E , Knust B , Naidoo D , Deen G , Formenty P , Nichol ST , Palacios G , Stroher U . Cell Rep 2018 22 (5) 1159-1168 ![]() ![]() Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutionary rates during persistence were either similar to or reduced relative to acute infection rates. Active EBOV replication/transcription continued during convalescence, but decreased over time, consistent with viral persistence rather than viral latency. Patterns of genetic divergence suggest a moderate relaxation of selective constraints within the sGP carboxy-terminal tail during persistent infections, but do not support widespread diversifying selection. Altogether, our data illustrate that EBOV persistence in semen, urine, and aqueous humor is not a quiescent or latent infection. |
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