Viruses

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12 pages, 969 KiB

Open AccessEditor’s ChoiceArticle

Bivalent VSV Vectors Mediate Rapid and Potent Protection from Andes Virus Challenge in Hamsters

by Joshua Marceau, David Safronetz, Cynthia Martellaro, Andrea Marzi, Kyle Rosenke and Heinz Feldmann

Viruses 2024, 16(2), 279; https://doi.org/10.3390/v16020279 - 11 Feb 2024

Viewed by 1415

Abstract

Orthohantaviruses may cause hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Andes virus (ANDV) is the only orthohantavirus associated with human–human transmission. Therefore, emergency vaccination would be a valuable public health measure to combat ANDV-derived infection clusters. Here, we utilized a promising [...] Read more.

Orthohantaviruses may cause hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Andes virus (ANDV) is the only orthohantavirus associated with human–human transmission. Therefore, emergency vaccination would be a valuable public health measure to combat ANDV-derived infection clusters. Here, we utilized a promising vesicular stomatitis virus (VSV)-based vaccine to advance the approach for emergency applications. We compared monovalent and bivalent VSV vectors containing the Ebola virus (EBOV), glycoprotein (GP), and ANDV glycoprotein precursor (GPC) for protective efficacy in pre-, peri- and post-exposure immunization by the intraperitoneal and intranasal routes. Inclusion of the EBOV GP was based on its favorable immune cell targeting and the strong innate responses elicited by the VSV-EBOV vaccine. Our data indicates no difference of ANDV GPC expressing VSV vectors in pre-exposure immunization independent of route, but a potential benefit of the bivalent VSVs following peri- and post-exposure intraperitoneal vaccination. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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18 pages, 2689 KiB

Open AccessArticle

Modeling the Immune Response for Pathogenic and Nonpathogenic Orthohantavirus Infections in Human Lung Microvasculature Endothelial Cells

by Evan P. Williams, Aadrita Nandi, Victoria Nam, Linda J. S. Allen, A. Alexandre Trindade, Michele M. Kosiewicz and Colleen B. Jonsson

Viruses 2023, 15(9), 1806; https://doi.org/10.3390/v15091806 - 24 Aug 2023

Viewed by 1315

Abstract

Hantaviruses, genus Orthohantavirus, family Hantaviridae, order Bunyavirales, are negative-sense, single-stranded, tri-segmented RNA viruses that persistently infect rodents, shrews, and moles. Of these, only certain virus species harbored by rodents are pathogenic to humans. Infection begins with inhalation of virus particles [...] Read more.

Hantaviruses, genus Orthohantavirus, family Hantaviridae, order Bunyavirales, are negative-sense, single-stranded, tri-segmented RNA viruses that persistently infect rodents, shrews, and moles. Of these, only certain virus species harbored by rodents are pathogenic to humans. Infection begins with inhalation of virus particles into the lung and trafficking to the lung microvascular endothelial cells (LMVEC). The reason why certain rodent-borne hantavirus species are pathogenic has long been hypothesized to be related to their ability to downregulate and dysregulate the immune response as well as increase vascular permeability of infected endothelial cells. We set out to study the temporal dynamics of host immune response modulation in primary human LMVECs following infection by Prospect Hill (nonpathogenic), Andes (pathogenic), and Hantaan (pathogenic) viruses. We measured the level of RNA transcripts for genes representing antiviral, proinflammatory, anti-inflammatory, and metabolic pathways from 12 to 72 h with time points every 12 h. Gene expression analysis in conjunction with mathematical modeling revealed a similar profile for all three viruses in terms of upregulated genes that partake in interferon signaling (TLR3, IRF7, IFNB1), host immune cell recruitment (CXCL10, CXCL11, and CCL5), and host immune response modulation (IDO1). We examined secreted protein levels of IFN-β, CXCL10, CXCL11, CCL5, and IDO in two male and two female primary HLMVEC donors at 48 and 60 h post infection. All three viruses induced similar levels of CCL5, CXCL10, and CXCL11 within a particular donor, and the levels were similar in three of the four donors. All three viruses induced different protein secretion levels for both IFN-β and IDO and secretion levels differed between donors. In conclusion, we show that there was no difference in the transcriptional profiles of key genes in primary HLMVECs following infection by pathogenic and nonpathogenic hantaviruses, with protein secretion levels being more donor-specific than virus-specific. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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19 pages, 1798 KiB

Open AccessArticle

Deep Sequencing to Reveal Phylo-Geographic Relationships of Juquitiba Virus in Paraguay

by Evans Ifebuche Nnamani, Briana Spruill-Harrell, Evan Peter Williams, Mariah K. Taylor, Robert D. Owen and Colleen B. Jonsson

Viruses 2023, 15(9), 1798; https://doi.org/10.3390/v15091798 - 24 Aug 2023

Viewed by 1662

Abstract

Several hantaviruses result in zoonotic infections of significant public health concern, causing hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in the Old and New World, respectively. Given a 35% case fatality rate, disease-causing New World hantaviruses require a greater [...] Read more.

Several hantaviruses result in zoonotic infections of significant public health concern, causing hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in the Old and New World, respectively. Given a 35% case fatality rate, disease-causing New World hantaviruses require a greater understanding of their biology, genetic diversity, and geographical distribution. Juquitiba hantaviruses have been identified in Oligoryzomys nigripes in Brazil, Paraguay, and Uruguay. Brazil has reported the most HCPS cases associated with this virus. We used a multiplexed, amplicon-based PCR strategy to screen and deep-sequence the virus harbored within lung tissues collected from Oligoryzomys species during rodent field collections in southern (Itapúa) and western (Boquerón) Paraguay. No Juquitiba-like hantaviruses were identified in Boquerón. Herein, we report the full-length S and M segments of the Juquitiba hantaviruses identified in Paraguay from O. nigripes. We also report the phylogenetic relationships of the Juquitiba hantaviruses in rodents collected from Itapúa with those previously collected in Canindeyú. We showed, using the TN93 nucleotide substitution model, the coalescent (constant-size) population tree model, and Bayesian inference implemented in the Bayesian evolutionary analysis by sampling trees (BEAST) framework, that the Juquitiba virus lineage in Itapúa is distinct from that in Canindeyú. Our spatiotemporal analysis showed significantly different time to the most recent ancestor (TMRA) estimates between the M and S segments, but a common geographic origin. Our estimates suggest the additional geographic diversity of the Juquitiba virus within the Interior Atlantic Forest and highlight the need for more extensive sampling across this biome. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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13 pages, 3755 KiB

Open AccessArticle

Differences in the Susceptibility of Human Tubular Epithelial Cells for Infection with Orthohantaviruses

by Pamela Schreiber, Ann-Kathrin Friedrich, Gefion Gruber, Christian Nusshag, Lukas Boegelein, Sandra Essbauer, Josephine Uhrig, Martin Zeier and Ellen Krautkrämer

Viruses 2023, 15(8), 1670; https://doi.org/10.3390/v15081670 - 31 Jul 2023

Cited by 1 | Viewed by 1241

Abstract

Diseases induced by infection with pathogenic orthohantaviruses are characterized by a pronounced organ-specific manifestation. Pathogenic Eurasian orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) with often massive proteinuria. Therefore, the use of a relevant kidney cell culture would be favorable to analyze the [...] Read more.

Diseases induced by infection with pathogenic orthohantaviruses are characterized by a pronounced organ-specific manifestation. Pathogenic Eurasian orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) with often massive proteinuria. Therefore, the use of a relevant kidney cell culture would be favorable to analyze the underlying cellular mechanisms of orthohantavirus-induced acute kidney injury (AKI). We tested different human tubular epithelial cell lines for their suitability as an in vitro infection model. Permissiveness and replication kinetics of highly pathogenic Hantaan virus (HTNV) and non-/low-pathogenic Tula virus (TULV) were analyzed in tubular epithelial cell lines and compared to human primary tubular epithelial cells. Ana-lysis of the cell line HK-2 revealed the same results for viral replication, morphological and functional effects as observed for HTNV in primary cells. In contrast, the cell lines RPTEC/TERT1 and TH1 demonstrated only poor infection rates after inoculation with HTNV and are unusable as an infection model. While pathogenic HNTV infects primary tubular and HK-2 cells, non-/low-pathogenic TULV infects neither primary tubular cells nor the cell line HK-2. Our results show that permissiveness of renal cells varies between orthohantaviruses with differences in pathogenicity and that HK-2 cells demonstrate a suitable in vitro model to study viral tropism and pathogenesis of orthohantavirus-induced AKI. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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10 pages, 1142 KiB

Open AccessCommunication

A Development of Rapid Whole-Genome Sequencing of Seoul orthohantavirus Using a Portable One-Step Amplicon-Based High Accuracy Nanopore System

by Kyungmin Park, Juyoung Noh, Kijin Kim, Jongwoo Kim, Hee-Kyung Cho, Seong-Gyu Kim, Eunyoung Yang, Won-Keun Kim and Jin-Won Song

Viruses 2023, 15(7), 1542; https://doi.org/10.3390/v15071542 - 13 Jul 2023

Cited by 1 | Viewed by 2329

Abstract

Whole-genome sequencing provides a robust platform for investigating the epidemiology and transmission of emerging viruses. Oxford Nanopore Technologies allows for real-time viral sequencing on a local laptop system for point-of-care testing. Seoul orthohantavirus (Seoul virus, SEOV), harbored by Rattus norvegicus and R. rattus [...] Read more.

Whole-genome sequencing provides a robust platform for investigating the epidemiology and transmission of emerging viruses. Oxford Nanopore Technologies allows for real-time viral sequencing on a local laptop system for point-of-care testing. Seoul orthohantavirus (Seoul virus, SEOV), harbored by Rattus norvegicus and R. rattus, causes mild hemorrhagic fever with renal syndrome and poses an important threat to public health worldwide. We evaluated the deployable MinION system to obtain high-fidelity entire-length sequences of SEOV for the genome identification of accurate infectious sources and their genetic diversity. One-step amplicon-based nanopore sequencing was performed from SEOV 80–39 specimens with different viral copy numbers and SEOV-positive wild rats. The KU-ONT-SEOV-consensus module was developed to analyze SEOV genomic sequences generated from the nanopore system. Using amplicon-based nanopore sequencing and the KU-ONT-consensus pipeline, we demonstrated novel molecular diagnostics for acquiring full-length SEOV genome sequences, with sufficient read depth in less than 6 h. The consensus sequence accuracy of the SEOV small, medium, and large genomes showed 99.75–100% (for SEOV 80–39 isolate) and 99.62–99.89% (for SEOV-positive rats) identities. This study provides useful insights into on-site diagnostics based on nanopore technology and the genome epidemiology of orthohantaviruses for a quicker response to hantaviral outbreaks. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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14 pages, 1589 KiB

Open AccessArticle

Hantavirus in Panama: Twenty Years of Epidemiological Surveillance Experience

by Blas Armién, Carlos Muñoz, Hector Cedeño, Jacqueline R. Salazar, Tybbyssay P. Salinas, Publio González, José Trujillo, Deyanira Sánchez, Jamileth Mariñas, Ayvar Hernández, Harmodio Cruz, Leisy Yovany Villarreal, Elba Grimaldo, Samuel González, Heydy Nuñez, Susana Hesse, Fernando Rivera, George Edwards, Ricardo Chong, Ovidio Mendoza, Martín Meza, Milagro Herrera, Rudick Kant, Raul Esquivel, Dora Estripeaut, Demetrio Serracín, Bernardino Denis, Esthefani Robles, Yaxelis Mendoza, Gloria Gonzalez, Felicia Tulloch, Juan Miguel Pascale, Jonathan L. Dunnum, Joseph A. Cook, Anibal G. Armién, Fernando Gracia, Gladys Alicia Guerrero and Itza de Mosca Show full author list Hide full author list

Viruses 2023, 15(6), 1395; https://doi.org/10.3390/v15061395 - 19 Jun 2023

Cited by 7 | Viewed by 2719

Abstract

Twenty years have passed since the emergence of hantavirus zoonosis in Panama at the beginning of this millennium. We provide an overview of epidemiological surveillance of hantavirus disease (hantavirus pulmonary syndrome and hantavirus fever) during the period 1999–2019 by including all reported and [...] Read more.

Twenty years have passed since the emergence of hantavirus zoonosis in Panama at the beginning of this millennium. We provide an overview of epidemiological surveillance of hantavirus disease (hantavirus pulmonary syndrome and hantavirus fever) during the period 1999–2019 by including all reported and confirmed cases according to the case definition established by the health authority. Our findings reveal that hantavirus disease is a low-frequency disease, affecting primarily young people, with a relatively low case-fatality rate compared to other hantaviruses in the Americas (e.g., ANDV and SNV). It presents an annual variation with peaks every 4–5 years and an interannual variation influenced by agricultural activities. Hantavirus disease is endemic in about 27% of Panama, which corresponds to agroecological conditions that favor the population dynamics of the rodent host, Oligoryzomys costaricensis and the virus (Choclo orthohantavirus) responsible for hantavirus disease. However, this does not rule out the existence of other endemic areas to be characterized. Undoubtedly, decentralization of the laboratory test and dissemination of evidence-based surveillance guidelines and regulations have standardized and improved diagnosis, notification at the level of the primary care system, and management in intensive care units nationwide. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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15 pages, 2530 KiB

Open AccessArticle

Two Decades of Wildlife Pathogen Surveillance: Case Study of Choclo orthohantavirus and Its Wild Reservoir Oligoryzomys costaricensis

by Publio Gonzalez, Jacqueline R. Salazar, Tybbysay P. Salinas, Mario Avila, Jocelyn P. Colella, Jonathan L. Dunnum, Gregory E. Glass, Gloria Gonzalez, Enos Juarez, Kimberly Lindblade, Edwin Pile, Yaxelis Mendoza, Juan Miguel Pascale, Anibal G. Armien, Joseph A. Cook and Blas Armien

Viruses 2023, 15(6), 1390; https://doi.org/10.3390/v15061390 - 17 Jun 2023

Cited by 4 | Viewed by 2239

Abstract

The Costa Rican pygmy rice rat (Oligoryzomys costaricensis) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically [...] Read more.

The Costa Rican pygmy rice rat (Oligoryzomys costaricensis) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically sampled and archived rodents from >150 sites across Panama to establish a baseline understanding of the host and virus, producing a permanent archive of holistic specimens that we are now probing in greater detail. We summarize these collections and explore preliminary habitat/virus associations to guide future wildlife surveillance and public health efforts related to CHOV and other zoonotic pathogens. Host sequences of the mitochondrial cytochrome b gene form a single monophyletic clade in Panama, despite wide distribution across Panama. Seropositive samples were concentrated in the central region of western Panama, consistent with the ecology of this agricultural commensal and the higher incidence of CHOV in humans in that region. Hantavirus seroprevalence in the pygmy rice rat was >15% overall, with the highest prevalence in agricultural areas (21%) and the lowest prevalence in shrublands (11%). Host–pathogen distribution, transmission dynamics, genomic evolution, and habitat affinities can be derived from the preserved samples, which include frozen tissues, and now provide a foundation for expanded investigations of orthohantaviruses in Panama. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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14 pages, 1594 KiB

Open AccessArticle

Multiple Lineages of Hantaviruses Harbored by the Iberian Mole (Talpa occidentalis) in Spain

by Se Hun Gu, Marcos Miñarro, Carlos Feliu, Jean-Pierre Hugot, Naomi L. Forrester, Scott C. Weaver and Richard Yanagihara

Viruses 2023, 15(6), 1313; https://doi.org/10.3390/v15061313 - 2 Jun 2023

Cited by 1 | Viewed by 2329

Abstract

The recent detection of both Nova virus (NVAV) and Bruges virus (BRGV) in European moles (Talpa europaea) in Belgium and Germany prompted a search for related hantaviruses in the Iberian mole (Talpa occidentalis). RNAlater^®-preserved lung tissue from [...] Read more.

The recent detection of both Nova virus (NVAV) and Bruges virus (BRGV) in European moles (Talpa europaea) in Belgium and Germany prompted a search for related hantaviruses in the Iberian mole (Talpa occidentalis). RNAlater^®-preserved lung tissue from 106 Iberian moles, collected during January 2011 to June 2014 in Asturias, Spain, were analyzed for hantavirus RNA by nested/hemi-nested RT-PCR. Pairwise alignment and comparison of partial L-segment sequences, detected in 11 Iberian moles from four parishes, indicated the circulation of genetically distinct hantaviruses. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, demonstrated three distinct hantaviruses in Iberian moles: NVAV, BRGV, and a new hantavirus, designated Asturias virus (ASTV). Of the cDNA from seven infected moles processed for next generation sequencing using Illumina HiSeq1500, one produced viable contigs, spanning the S, M and L segments of ASTV. The original view that each hantavirus species is harbored by a single small-mammal host species is now known to be invalid. Host-switching or cross-species transmission events, as well as reassortment, have shaped the complex evolutionary history and phylogeography of hantaviruses such that some hantavirus species are hosted by multiple reservoir species, and conversely, some host species harbor more than one hantavirus species. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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14 pages, 752 KiB

Open AccessArticle

Hantavirus Infection in Children—A Pilot Study of Single Regional Center

by Adriana Mocanu, Ana-Maria Cajvan, Tudor Ilie Lazaruc, Vasile Valeriu Lupu, Laura Florescu, Ancuta Lupu, Roxana Alexandra Bogos, Ileana Ioniuc, Georgiana Scurtu, Felicia Dragan and Iuliana Magdalena Starcea

Viruses 2023, 15(4), 872; https://doi.org/10.3390/v15040872 - 29 Mar 2023

Cited by 1 | Viewed by 1934

Abstract

Background: Hantaviruses are infectious etiological agents of a group of rodent-borne hemorrhagic fevers, with two types of clinical manifestations in humans: hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). According to available statistics, the disease occurs mainly in adults, but [...] Read more.

Background: Hantaviruses are infectious etiological agents of a group of rodent-borne hemorrhagic fevers, with two types of clinical manifestations in humans: hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). According to available statistics, the disease occurs mainly in adults, but the lower incidence in the pediatric population might also be related to a lack of diagnosis possibilities or even unsatisfactory knowledge about the disease. Materials and Methods: The purpose of this study was to evaluate the cases of hemorrhagic fever with renal syndrome diagnosed and treated in the Department of Nephrology at St. Mary’s Emergency Hospital for Children in Iasi, Romania, representative of the North-East of Romania. We also reviewed the specialized literature on the topic. Results: Between January 2017 and January 2022, eight cases of HFRS, all men, and seven from rural areas, aged 11–18 years old, were referred to our clinic because of an acute kidney injury (AKI). Seven cases were identified as Dobrava serotype while one case was determined by Haantan serotype. Conclusions: HFRS should always be considered as a differential diagnosis when faced with a patient with AKI and thrombocytopenia. Dobrava serotype is the most common hantavirus subtype in the Balkans. For the specific prevention of human infections, mainly in high-risk groups, vaccines are needed. As far as we know, this is the first study on HFRS in Romanian children. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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12 pages, 551 KiB

Open AccessArticle

Seroprevalence of Hantavirus in Forestry Workers, Northern France, 2019–2020

by Catarina Krug, Emma Rigaud, Dieyenaba Siby-Diakite, Laetitia Bénézet, Pavlos Papadopoulos, Henriette de Valk, Gaëtan Deffontaines, Alexandra Septfons and Jean-Marc Reynes

Viruses 2023, 15(2), 338; https://doi.org/10.3390/v15020338 - 25 Jan 2023

Cited by 5 | Viewed by 2068

Abstract

We aimed to estimate the seroprevalence of Puumala orthohantavirus (PUUV) among forestry workers in northern France, and to explore sociodemographic risk factors. We conducted a random cross-sectional seroprevalence survey among 1777 forestry workers in 2019–2020. The presence of immunoglobulin G against PUUV antigens [...] Read more.

We aimed to estimate the seroprevalence of Puumala orthohantavirus (PUUV) among forestry workers in northern France, and to explore sociodemographic risk factors. We conducted a random cross-sectional seroprevalence survey among 1777 forestry workers in 2019–2020. The presence of immunoglobulin G against PUUV antigens in serum was assessed using enzyme-linked immunosorbent assay and confirmed using immunofluorescence assay. Poisson regression models were used to explore factors associated with seropositivity. Weighted seroprevalence was 5% (3–6) in northeastern France, 4% (2–6) in north central France, and 1% in two regions located in the center of the country (Auvergne and Limousin). There were no seropositive workers detected in northwestern France. Seropositivity was associated with age, sex, and cumulative seniority in the forestry sector. Seroprevalence was highest in known endemic areas of the northeast and lowest in the northwest. Nevertheless, we found serological evidence of PUUV infection in two regions located in the center of the country, suggesting circulation of the virus in these regions, previously thought to be non-endemic. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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Review

Jump to: Research, Other

13 pages, 3622 KiB

Open AccessReview

Cases of Hemorrhagic Fever with Renal Syndrome in Russia during 2000–2022

by Evgeniy Tkachenko, Svetlana Kurashova, Alexandra Balkina, Alexander Ivanov, Mariya Egorova, Oksana Leonovich, Yulia Popova, Rostislav Teodorovich, Alla Belyakova, Petr Tkachenko, Dmitriy Trankvilevsky, Ekaterina Blinova, Aydar Ishmukhametov and Tamara Dzagurova

Viruses 2023, 15(7), 1537; https://doi.org/10.3390/v15071537 - 12 Jul 2023

Cited by 7 | Viewed by 2147

Abstract

During 2000–2022, a total of 69 of Russia’s 85 administrative regions reported 164,580 hemorrhagic fever with renal syndrome (HFRS) cases, with an annual average rate of 4.9 cases/100,000 population (10⁵ popul.). European Russia reported 162,045 (98.5%) cases in 53/60 regions with 9.7 [...] Read more.

During 2000–2022, a total of 69 of Russia’s 85 administrative regions reported 164,580 hemorrhagic fever with renal syndrome (HFRS) cases, with an annual average rate of 4.9 cases/100,000 population (10⁵ popul.). European Russia reported 162,045 (98.5%) cases in 53/60 regions with 9.7 cases/10⁵ popul. Asian Russia reported 2535 (1.5%) cases in 16/25 regions with 0.6 cases/10⁵ popul. In the same period, Russia reported 668 (0.4%) fatal HFRS cases, and 4030 (2.4%) cases among children under the age of 14 years. Most HFRS cases occurred during autumn and winter. The incidence among rural residents was 6.7 per 10⁵ popul., higher than the urban 4.4 per 10⁵ popul.; however, among HFRS patients, rural and urban residents account for 35% and 65%, respectively. Six hantaviruses, causing HFRS of different clinical severity, were recognized as pathogens: Hantaan (HTNV) and Amur (AMUV) of Orthohantavirus hantanense species, Seoul (SEOV) of Orthohantavirus seoulense species, Puumala (PUUV) of Orthohantavirus puumalaense species, and Kurkino (KURV) and Sochi (SOCV) of Orthohantavirus dobravaense species, with the principal hosts Apodemus agrarius coreae, Apodemus peninsulae, Rattus norvegicus, Myodes glareolus, Apodemus agrarius agrarius, and Sylvaemus ponticus, respectively. It was found that 97.7% of HFRS cases are caused by PUUV, therefore, this virus plays the main role in the HFRS morbidity structure in Russia. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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18 pages, 388 KiB

Open AccessReview

Orthohantavirus Replication in the Context of Innate Immunity

by Autumn LaPointe, Michael Gale, Jr. and Alison M. Kell

Viruses 2023, 15(5), 1130; https://doi.org/10.3390/v15051130 - 9 May 2023

Viewed by 2599

Abstract

Orthohantaviruses are rodent-borne, negative-sense RNA viruses that are capable of causing severe vascular disease in humans. Over the course of viral evolution, these viruses have tailored their replication cycles in such a way as to avoid and/or antagonize host innate immune responses. In [...] Read more.

Orthohantaviruses are rodent-borne, negative-sense RNA viruses that are capable of causing severe vascular disease in humans. Over the course of viral evolution, these viruses have tailored their replication cycles in such a way as to avoid and/or antagonize host innate immune responses. In the rodent reservoir, this results in life long asymptomatic infections. However, in hosts other than its co-evolved reservoir, the mechanisms for subduing the innate immune response may be less efficient or absent, potentially leading to disease and/or viral clearance. In the case of human orthohantavirus infection, the interaction of the innate immune response with viral replication is thought to give rise to severe vascular disease. The orthohantavirus field has made significant advancements in understanding how these viruses replicate and interact with host innate immune responses since their identification by Dr. Ho Wang Lee and colleagues in 1976. Therefore, the purpose of this review, as part of this special issue dedicated to Dr. Lee, was to summarize the current knowledge of orthohantavirus replication, how viral replication activates innate immunity, and how the host antiviral response, in turn, impacts viral replication. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

Other

Jump to: Research, Review

17 pages, 1540 KiB

Open AccessPerspective

Forecasting Outbreaks of Hantaviral Disease: Future Directions in Geospatial Modeling

by Gregory E. Glass

Viruses 2023, 15(7), 1461; https://doi.org/10.3390/v15071461 - 28 Jun 2023

Viewed by 1239

Abstract

Hantaviral diseases have been recognized as ‘place diseases’ from their earliest identification and, epidemiologically, are tied to single host species with transmission occurring from infectious hosts to humans. As such, human populations are most at risk when they are in physical proximity to [...] Read more.

Hantaviral diseases have been recognized as ‘place diseases’ from their earliest identification and, epidemiologically, are tied to single host species with transmission occurring from infectious hosts to humans. As such, human populations are most at risk when they are in physical proximity to suitable habitats for reservoir populations, when numbers of infectious hosts are greatest. Because of the lags between improving habitat conditions and increasing infectious host abundance and spillover to humans, it should be possible to anticipate (forecast) where and when outbreaks will most likely occur. Most mammalian hosts are associated with specific habitat requirements, so identifying these habitats and the ecological drivers that impact population growth and the dispersal of viral hosts should be markers of the increased risk for disease outbreaks. These regions could be targeted for public health and medical education. This paper outlines the rationale for forecasting zoonotic outbreaks, and the information that needs to be clarified at various levels of biological organization to make the forecasting of orthohantaviruses successful. Major challenges reflect the transdisciplinary nature of forecasting zoonoses, with needs to better understand the implications of the data collected, how collections are designed, and how chosen methods impact the interpretation of results. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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11 pages, 953 KiB

Open AccessOpinion

The Power of We

by James W. Le Duc

Viruses 2023, 15(4), 921; https://doi.org/10.3390/v15040921 - 5 Apr 2023

Cited by 2 | Viewed by 1509

Abstract

“The Power of We” is a personal tribute to the individuals and organizations that collaborated in the discovery and advancement of knowledge of the hantaviruses following the original isolation of Hantaan virus by Ho Wang Lee. It focuses on the work done primarily [...] Read more.

“The Power of We” is a personal tribute to the individuals and organizations that collaborated in the discovery and advancement of knowledge of the hantaviruses following the original isolation of Hantaan virus by Ho Wang Lee. It focuses on the work done primarily at the United States Army Medical Research Institute of Infectious Diseases during the decade of the 1980s under the leadership of Joel Dalrymple, who worked in close partnership with Ho Wang Lee. These early studies helped define the global distribution of Seoul virus and provided seminal information on its maintenance and transmission among urban rats. Other collaborations involved partners in Europe, Asia, and Latin America and resulted in the isolation of novel hantaviruses, a better understanding of their global distribution, and validation of diagnostics and therapeutic interventions for treatment of human diseases. By working in partnership, scientists from around the world made critical discoveries that led to a better understanding of the hantaviruses. “The Power of We” demonstrates that we all benefit when we work together with a shared vision, a common commitment to excellence, and mutual respect. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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9 pages, 271 KiB

Open AccessOpinion

Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome

by Antti Vaheri, Teemu Smura, Hanna Vauhkonen, Jussi Hepojoki, Tarja Sironen, Tomas Strandin, Johanna Tietäväinen, Tuula Outinen, Satu Mäkelä, Ilkka Pörsti and Jukka Mustonen

Viruses 2023, 15(3), 805; https://doi.org/10.3390/v15030805 - 22 Mar 2023

Cited by 7 | Viewed by 2085

Abstract

The clinical outcome of Puumala hantavirus (PUUV) infection shows extensive variation, ranging from inapparent subclinical infection (70–80%) to severe hemorrhagic fever with renal syndrome (HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience acute kidney injury (AKI), histologically known as [...] Read more.

The clinical outcome of Puumala hantavirus (PUUV) infection shows extensive variation, ranging from inapparent subclinical infection (70–80%) to severe hemorrhagic fever with renal syndrome (HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience acute kidney injury (AKI), histologically known as acute hemorrhagic tubulointerstitial nephritis. Why this variation? There is no evidence that there would be more virulent and less virulent variants infecting humans, although this has not been extensively studied. Individuals with the human leukocyte antigen (HLA) alleles B*08 and DRB1*0301 are likely to have a severe form of the PUUV infection, and those with B*27 are likely to have a benign clinical course. Other genetic factors, related to the tumor necrosis factor (TNF) gene and the C4A component of the complement system, may be involved. Various autoimmune phenomena and Epstein-Barr virus infection are associated with PUUV infection, but hantavirus-neutralizing antibodies are not associated with lower disease severity in PUUV HFRS. Wide individual differences occur in ocular and central nervous system (CNS) manifestations and in the long-term consequences of nephropathia epidemica (NE). Numerous biomarkers have been detected, and some are clinically used to assess and predict the severity of PUUV infection. A new addition is the plasma glucose concentration associated with the severity of both capillary leakage, thrombocytopenia, inflammation, and AKI in PUUV infection. Our question, “Why this variation?” remains largely unanswered. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

12 pages, 446 KiB

Open AccessCommentary

Pending Reorganization of Hantaviridae to Include Only Completely Sequenced Viruses: A Call to Action

by Jens H. Kuhn, Steven B. Bradfute, Charles H. Calisher, Boris Klempa, Jonas Klingström, Lies Laenen, Gustavo Palacios, Connie S. Schmaljohn, Nicole D. Tischler and Piet Maes

Viruses 2023, 15(3), 660; https://doi.org/10.3390/v15030660 - 28 Feb 2023

Cited by 12 | Viewed by 2648

Abstract

The official classification of newly discovered or long-known unassigned viruses by the International Committee on Taxonomy of Viruses (ICTV) requires the deposition of coding-complete or -near-complete virus genome sequences in GenBank to fulfill a requirement of the taxonomic proposal (TaxoProp) process. However, this [...] Read more.

The official classification of newly discovered or long-known unassigned viruses by the International Committee on Taxonomy of Viruses (ICTV) requires the deposition of coding-complete or -near-complete virus genome sequences in GenBank to fulfill a requirement of the taxonomic proposal (TaxoProp) process. However, this requirement is fairly new; thus, genomic sequence information is fragmented or absent for many already-classified viruses. As a result, taxon-wide modern phylogenetic analyses are often challenging, if not impossible. This problem is particularly eminent among viruses with segmented genomes, such as bunyavirals, which were frequently classified solely based on single-segment sequence information. To solve this issue for one bunyaviral family, Hantaviridae, we call on the community to provide additional sequence information for incompletely sequenced classified viruses by mid-June 2023. Such sequence information may be sufficient to prevent their possible declassification during the ongoing efforts to establish a coherent, consistent, and evolution-based hantavirid taxonomy. Full article

(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)

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