Strengthening the Interaction of the Virology Community with the International Committee on Taxonomy of Viruses (ICTV) by Linking Virus Names and Their Abbreviations to Virus Species.

The International Committee on Taxonomy of Viruses (ICTV) is tasked with classifying viruses into taxa (phyla to species) and devising taxon names. Virus names and virus name abbreviations are currently not within the ICTV's official remit and are not regulated by an official entity. Many scientists, medical/veterinary professionals, and regulatory agencies do not address evolutionary questions nor are they concerned with the hierarchical organization of the viral world, and therefore, have limited use for ICTV-devised taxa. Instead, these professionals look to the ICTV as an expert point source that provides the most current taxonomic affiliations of viruses of interests to facilitate document writing. These needs are currently unmet as an ICTV-supported, easily searchable database that includes all published virus names and abbreviations linked to their taxa is not available. In addition, in stark contrast to other biological taxonomic frameworks, virus taxonomy currently permits individual species to have several members. Consequently, confusion emerges among those who are not aware of the difference between taxa and viruses, and because certain well-known viruses cannot be located in ICTV publications or be linked to their species. In addition, the number of duplicate names and abbreviations has increased dramatically in the literature. To solve this conundrum, the ICTV could mandate listing all viruses of established species and all reported unclassified viruses in forthcoming online ICTV Reports and create a searchable webpage using this information. The International Union of Microbiology Societies could also consider changing the mandate of the ICTV to include the nomenclature of all viruses in addition to taxon considerations. With such a mandate expansion, official virus names and virus name abbreviations could be catalogued and virus nomenclature could be standardized. As a result, the ICTV would become an even more useful resource for all stakeholders in virology.

RNA viruses can hijack vertebrate microRNAs to suppress innate immunity.

Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses. This is primarily attributed to the ease with which these viruses mutate to disrupt recognition and growth suppression by host miRNAs. Here we report that the haematopoietic-cell-specific miRNA miR-142-3p potently restricts the replication of the mosquito-borne North American eastern equine encephalitis virus in myeloid-lineage cells by binding to sites in the 3' non-translated region of its RNA genome. However, by limiting myeloid cell tropism and consequent innate immunity induction, this restriction directly promotes neurologic disease manifestations characteristic of eastern equine encephalitis virus infection in humans. Furthermore, the region containing the miR-142-3p binding sites is essential for efficient virus infection of mosquito vectors. We propose that RNA viruses can adapt to use antiviral properties of vertebrate miRNAs to limit replication in particular cell types and that this restriction can lead to exacerbation of disease severity.

High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus.

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present.

Eastern equine encephalitis in Latin America.

BACKGROUND: The eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE) viruses are pathogens that infect humans and horses in the Americas. Outbreaks of neurologic disease in humans and horses were reported in Panama from May through early August 2010. METHODS: We performed antibody assays and tests to detect viral RNA and isolate the viruses in serum samples from hospitalized patients. Additional cases were identified with enhanced surveillance. RESULTS: A total of 19 patients were hospitalized for encephalitis. Among them, 7 had confirmed EEE, 3 had VEE, and 1 was infected with both viruses; 3 patients died, 1 of whom had confirmed VEE. The clinical findings for patients with EEE included brain lesions, seizures that evolved to status epilepticus, and neurologic sequelae. An additional 99 suspected or probable cases of alphavirus infection were detected during active surveillance. In total, 13 cases were confirmed as EEE, along with 11 cases of VEE and 1 case of dual infection. A total of 50 cases in horses were confirmed as EEE and 8 as VEE; mixed etiologic factors were associated with 11 cases in horses. Phylogenetic analyses of isolates from 2 cases of equine infection with the EEE virus and 1 case of human infection with the VEE virus indicated that the viruses were of enzootic lineages previously identified in Panama rather than new introductions. CONCLUSIONS: Cases of EEE in humans in Latin America may be the result of ecologic changes that increased human contact with enzootic transmission cycles, genetic changes in EEE viral strains that resulted in increased human virulence, or an altered host range. (Funded by the National Institutes of Health and the Secretaría Nacional de Ciencia, Tecnología e Innovación, Panama.).

First Record of Aedes albopictus in Georgia and Updated Checklist of Reported Species.

Mosquito surveillance was carried out in Batumi, Georgia, in August 2014. Aedes albopictus was detected for the first time, which brought the number of reported mosquito species in Georgia to 32. An updated checklist of the mosquitoes of Georgia is provided.

Negevirus: a proposed new taxon of insect-specific viruses with wide geographic distribution.

Six novel insect-specific viruses, isolated from mosquitoes and phlebotomine sand flies collected in Brazil, Peru, the United States, Ivory Coast, Israel, and Indonesia, are described. Their genomes consist of single-stranded, positive-sense RNAs with poly(A) tails. By electron microscopy, the virions appear as spherical particles with diameters of ∼45 to 55 nm. Based on their genome organization and phylogenetic relationship, the six viruses, designated Negev, Ngewotan, Piura, Loreto, Dezidougou, and Santana, appear to form a new taxon, tentatively designated Negevirus. Their closest but still distant relatives are citrus leposis virus C (CiLV-C) and viruses in the genus Cilevirus, which are mite-transmitted plant viruses. The negeviruses replicate rapidly and to high titer (up to 10(10) PFU/ml) in mosquito cells, producing extensive cytopathic effect and plaques, but they do not appear to replicate in mammalian cells or mice. A discussion follows on their possible biological significance and effect on mosquito vector competence for arboviruses.

African Green Monkeys Maintain Zika Virus Neutralizing Antibodies for at Least 1,427 Days Postinfection.

We report strong Zika virus (ZIKV) neutralizing antibody responses in African green monkeys (Chlorocebus sabaeus) up to 1,427 days after ZIKV exposure via the subcutaneous, intravaginal, or intrarectal routes. Our results suggest that immunocompetent African green monkeys previously infected with ZIKV are likely protected from reinfection for years, possibly life, and would not contribute to virus amplification during ZIKV epizootics.

Construction and organization of a BSL-3 cryo-electron microscopy laboratory at UTMB.

A unique cryo-electron microscopy facility has been designed and constructed at the University of Texas Medical Branch (UTMB) to study the three-dimensional organization of viruses and bacteria classified as select agents at biological safety level (BSL)-3, and their interactions with host cells. A 200keV high-end cryo-electron microscope was installed inside a BSL-3 containment laboratory and standard operating procedures were developed and implemented to ensure its safe and efficient operation. We also developed a new microscope decontamination protocol based on chlorine dioxide gas with a continuous flow system, which allowed us to expand the facility capabilities to study bacterial agents including spore-forming species. The new unified protocol does not require agent-specific treatment in contrast to the previously used heat decontamination. To optimize the use of the cryo-electron microscope and to improve safety conditions, it can be remotely controlled from a room outside of containment, or through a computer network world-wide. Automated data collection is provided by using JADAS (single particle imaging) and SerialEM (tomography). The facility has successfully operated for more than a year without an incident and was certified as a select agent facility by the Centers for Disease Control.

The structure of barmah forest virus as revealed by cryo-electron microscopy at a 6-angstrom resolution has detailed transmembrane protein architecture and interactions.

Barmah Forest virus (BFV) is a mosquito-borne alphavirus that infects humans. A 6-Å-resolution cryo-electron microscopy three-dimensional structure of BFV exhibits a typical alphavirus organization, with RNA-containing nucleocapsid surrounded by a bilipid membrane anchored with the surface proteins E1 and E2. The map allows details of the transmembrane regions of E1 and E2 to be seen. The C-terminal end of the E2 transmembrane helix binds to the capsid protein. Following the E2 transmembrane helix, a short α-helical endodomain lies on the inner surface of the lipid envelope. The E2 endodomain interacts with E1 transmembrane helix from a neighboring E1-E2 trimeric spike, thereby acting as a spacer and a linker between spikes. In agreement with previous mutagenesis studies, the endodomain plays an important role in recruiting other E1-E2 spikes to the budding site during virus assembly. The E2 endodomain may thus serve as a target for antiviral drug design.

Ebola virus persistence and disease recrudescence in the brains of antibody-treated nonhuman primate survivors.

Effective therapeutics have been developed against acute Ebola virus disease (EVD) in both humans and experimentally infected nonhuman primates. However, the risk of viral persistence and associated disease recrudescence in survivors receiving these therapeutics remains unclear. In contrast to rhesus macaques that survived Ebola virus (EBOV) exposure in the absence of treatment, we discovered that EBOV, despite being cleared from all other organs, persisted in the brain ventricular system of rhesus macaque survivors that had received monoclonal antibody (mAb) treatment. In mAb-treated macaque survivors, EBOV persisted in macrophages infiltrating the brain ventricular system, including the choroid plexuses. This macrophage infiltration was accompanied by severe tissue damage, including ventriculitis, choroid plexitis, and meningoencephalitis. Specifically, choroid plexus endothelium-derived EBOV infection led to viral persistence in the macaque brain ventricular system. This resulted in apoptosis of ependymal cells, which constitute the blood-cerebrospinal fluid barrier of the choroid plexuses. Fatal brain-confined recrudescence of EBOV infection manifested as severe inflammation, local pathology, and widespread infection of the ventricular system and adjacent neuropil in some of the mAb-treated macaque survivors. This study highlights organ-specific EBOV persistence and fatal recrudescent disease in rhesus macaque survivors after therapeutic treatment and has implications for the long-term follow-up of human survivors of EVD.

Probable non-vector-borne transmission of Zika virus, Colorado, USA.

Clinical and serologic evidence indicate that 2 American scientists contracted Zika virus infections while working in Senegal in 2008. One of the scientists transmitted this arbovirus to his wife after his return home. Direct contact is implicated as the transmission route, most likely as a sexually transmitted infection.

The spatial epidemiology and clinical features of reported cases of La Crosse virus infection in West Virginia from 2003 to 2007.

BACKGROUND: La Crosse virus (LACV) is a major cause of pediatric encephalitis in the United States. Since the mid-1980s, the number of reported cases of LACV infection in West Virginia has continued to rise and the state currently reports the most cases in the United States. The purpose of this study was to investigate and describe the spatial epidemiology and clinical presentation of LACV infection cases reported in West Virginia, as well as to provide a description of the environmental conditions present at the residences of the LACV infection cases. METHODS: Descriptive and spatial analyses were performed on LACV infection cases reported to the West Virginia Department of Health from 2003 to 2007. Clinical and environmental variables were available for 96 cases and residence data were available for 68 of these cases. Spatial analyses using the global Moran's I and Kulldorff's spatial scan statistic were performed using the population 15 years and younger at both the county and census tract levels to identify those geographic areas at the highest risk of infection. RESULTS: Two statistically significant (p < 0.05) high-risk clusters, involving six counties, were detected at the county level. At the census tract level, one statistically significant high-risk cluster involving 41 census tracts spanning over six counties was identified. The county level cumulative incidence for those counties in the primary high-risk cluster ranged from 100.0 to 189.0 cases per 100,000 persons (median 189.0) and the census tract level cumulative incidence for those counties in the high-risk cluster ranged from 61.7 to 505.9 cases per 100,000 persons (median 99.0). The counties and census tracts within high-risk clusters had a relative risk four to nine times higher when compared to those areas not contained within high-risk clusters. The majority of LACV infection cases were reported during the summer months in children 15 years and younger. Fever, vomiting, photophobia, and nausea were the most commonly reported signs and symptoms. A case fatality rate (CFR) of 3.1% was observed. Wooded areas and containers were present at the majority of case residences. CONCLUSIONS: The cumulative incidences of LACV infection from 2003 to 2007 were considerably higher than previously reported for West Virginia, and statistically significant high-risk clusters for LACV infection were detected at both the county and census tract levels. The finding of a high CFR and the identification of those areas at highest risk for infection will be useful for guiding future research and intervention efforts.

Inaccuracies in Google's Health-Based Knowledge Panels Perpetuate Widespread Misconceptions Involving Infectious Disease Transmission.

Google health-based Knowledge Panels were designed to provide users with high-quality basic medical information on a specific condition. However, any errors contained within Knowledge Panels could result in the widespread distribution of inaccurate health information. We explored the potential for inaccuracies to exist within Google's health-based Knowledge Panels by focusing on a single well-studied pathogen, Ebola virus (EBOV). We then evaluated the accuracy of those transmission modes listed within the Google Ebola Knowledge Panel and investigated the pervasiveness of any misconceptions associated with inaccurate transmission modes among persons living in Africa. We found that the Google Ebola Knowledge Panel inaccurately listed insect bites or stings as modes of EBOV transmission. Our scoping review found 27 articles and reports that revealed that 9 of 11 countries where misconceptions regarding insect transmission of EBOV have been reported are locations of current (i.e., Democratic Republic of Congo and Guinea) or previous EBOV outbreaks. We found reports that up to 26.6% (155/582) of study respondents in Democratic Republic of Congo believed mosquito bite avoidance would prevent EBOV; in other locations of previous large-scale EBOV outbreaks (e.g., Guinea), up to 61.0% (304/498) of respondents believed insects were involved in EBOV transmission. Our findings highlight the potential for errors to exist within the health information contained in Google's health-based Knowledge Panels. Such errors could perpetuate misconceptions or misinformation, leading to mistrust of health workers and aid agencies and in turn undermining public health education or outbreak response efforts.

No Evidence of rVSV-Ebola Virus Vaccine Replication or Dissemination in the Sand Fly Phlebotomus papatasi.

Following vaccination with the live attenuated, recombinant vesicular stomatitis virus Indiana serotype Ebola virus (rVSV-EBOV) vaccine, persons may exhibit a transient vaccine-associated viremia. To investigate the potential for Old World sand flies to transmit this vaccine following feeding on a viremic person, we fed laboratory-reared Phlebotomus papatasi an artificial blood meal containing 7.2 log10 plaque-forming units of rVSV-EBOV. Replication or dissemination was not detected in the body or legs of any P. papatasi collected at seven (n = 75) or 15 (n = 75) days post-feed. These results indicate a low potential for rVSV-EBOV to replicate and disseminate in P. papatasi, a species whose geographic distribution ranges from Morocco to southwest Asia and as far north as southern Europe.

Novel viruses in hard ticks collected in the Republic of Korea unveiled by metagenomic high-throughput sequencing analysis.

Ticks are vectors of a wide range of zoonotic viruses of medical and veterinary importance. Recently, metagenomics studies demonstrated that they are also the source of potentially pathogenic novel viruses. During the period from 2015 to 2017, questing ticks were collected by dragging the vegetation from geographically distant locations in the Republic of Korea (ROK) and a target-independent high-throughput sequencing method was utilized to study their virome. A total of seven viruses, including six putative novel viral entities, were identified. Genomic analysis showed that the novel viruses were most closely related to members in the orders Jingchuvirales and Bunyavirales. Phylogenetic reconstruction showed that the Bunyavirales-like viruses grouped in the same clade with other viruses within the Nairovirus and Phlebovirus genera, while the novel Jingchuvirales-like virus grouped together with other viruses within the family Chuviridae. Real-time RT-PCR was used to determine the geographic distribution and prevalence of these viruses in adult ticks. These novel viruses have a wide geographic distribution in the ROK with prevalences ranging from 2% to 18%. Our study expands the knowledge about the composition of the tick virome and highlights the wide diversity of viruses they harbor in the ROK. The discovery of novel viruses associated with ticks in the ROK highlights the need for an active tick-borne disease surveillance program to identify possible reservoirs of putative novel human pathogens.

Modeling the Stability of SARS-CoV-2 on Personal Protective Equipment (PPE).

We modeled the stability of SARS-CoV-2 on personal protective equipment (PPE) commonly worn in hospitals when carrying out high-risk airway procedures. Evaluated PPE included the visors and hoods of two brands of commercially available powered air purifying respirators, a disposable face shield, and Tyvek coveralls. Following an exposure to 4.3 log10 plaque-forming units (PFUs) of SARS-CoV-2, all materials displayed a reduction in titer of > 4.2 log10 by 72 hours postexposure, with detectable titers at 72 hours varying by material (1.1-2.3 log10 PFU/mL). Our results highlight the need for proper doffing and disinfection of PPE, or disposal, to reduce the risk of SARS-CoV-2 contact or fomite transmission.

Modeling the stability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on skin, currency, and clothing.

A new coronavirus (SARS-CoV-2) emerged in the winter of 2019 in Wuhan, China, and rapidly spread around the world. The extent and efficiency of SARS-CoV-2 pandemic is far greater than previous coronaviruses that emerged in the 21st Century. Here, we modeled stability of SARS-CoV-2 on skin, paper currency, and clothing to determine if these surfaces may factor in the fomite transmission dynamics of SARS-CoV-2. Skin, currency, and clothing samples were exposed to SARS-CoV-2 under laboratory conditions and incubated at three different temperatures (4°C± 2°C, 22°C± 2°C, and 37°C ± 2°C). We evaluated stability at 0 hours (h), 4 h, 8 h, 24 h, 72 h, 96 h, 7 days, and 14 days post-exposure. SARS-CoV-2 was stable on skin through the duration of the experiment at 4°C (14 days). Virus remained stable on skin for at least 96 h at 22°C and for at least 8h at 37°C. There were minimal differences between the tested currency samples. The virus remained stable on the $1 U.S.A. Bank Note for at least 96 h at 4°C while we did not detect viable virus on the $20 U.S.A. Bank Note samples beyond 72 h. The virus remained stable on both Bank Notes for at least 8 h at 22°C and 4 h at 37°C. Clothing samples were similar in stability to the currency. Viable virus remained for at least 96 h at 4°C and at least 4 h at 22°C. We did not detect viable virus on clothing samples at 37°C after initial exposure. This study confirms the inverse relationship between virus stability and temperature. Furthermore, virus stability on skin demonstrates the need for continued hand hygiene practices to minimize fomite transmission both in the general population as well as in workplaces where close contact is common.