Laguna Negra Virus Infection Causes Hantavirus Pulmonary Syndrome in Turkish Hamsters (Mesocricetus brandti).

Laguna Negra virus (LNV) is a New World hantavirus associated with severe and often fatal cardiopulmonary disease in humans, known as hantavirus pulmonary syndrome (HPS). Five hamster species were evaluated for clinical and serologic responses following inoculation with 4 hantaviruses. Of the 5 hamster species, only Turkish hamsters infected with LNV demonstrated signs consistent with HPS and a fatality rate of 43%. Clinical manifestations in infected animals that succumbed to disease included severe and rapid onset of dyspnea, weight loss, leukopenia, and reduced thrombocyte numbers as compared to uninfected controls. Histopathologic examination revealed lung lesions that resemble the hallmarks of HPS in humans, including interstitial pneumonia and pulmonary edema, as well as generalized infection of endothelial cells and macrophages in major organ tissues. Histologic lesions corresponded to the presence of viral antigen in affected tissues. To date, there have been no small animal models available to study LNV infection and pathogenesis. The Turkish hamster model of LNV infection may be important in the study of LNV-induced HPS pathogenesis and development of disease treatment and prevention strategies.

Decontamination of common healthcare facility surfaces contaminated with SARS-CoV-2 using peracetic acid dry fogging.

BACKGROUND: The SARS-CoV-2 pandemic has highlighted the urgent need for safe and effective surface decontamination methods, particularly in healthcare settings. AIM: To evaluate the effectiveness of peracetic acid (PAA) dry fogging in decontaminating healthcare facility surfaces experimentally contaminated with SARS-CoV-2. METHODS: Nine materials (stainless steel, latex painted wood, unsealed hardwood, melamine countertop, vinyl flooring, clear plastic, faux leather, computer keyboard button, and smartphone touch screen) were surface contaminated with >106 median tissue culture infectious dose (TCID50) of SARS-CoV-2, and allowed to dry before exposing to PAA dry fogging. FINDINGS: When fumigated with PAA dry fog for 1 h, no infectious SARS-CoV-2 virus was recovered from any of the experimentally inoculated surface types. By contrast, high titres of infectious virus were recovered from corresponding untreated drying controls of the same materials. CONCLUSION: Standard surface decontamination processes, including sprays and wipes, are laborious and frequently cannot completely decontaminate sensitive electronic equipment. The ease of use, low cost, and overall effectiveness of a PAA dry fogging suggest that it should be considered for decontaminating healthcare settings, particularly intensive care units where severely ill SARS-CoV-2 patients are cared for.

Crimean-Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures.

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral zoonosis with a case-fatality rate ranging from 9% to 50% in humans. Although a licensed vaccine to prevent infection by the CCHF virus (CCHFV) exists, its ability to induce neutralizing antibodies is limited and its efficacy against CCHFV remains undetermined. In addition, controlling CCHF infections by eradication of the tick reservoir has been ineffective, both economically and logistically, and the treatment options for CCHF remain limited. In this review, we first critically discuss the existing animal models to evaluate therapeutics for CCHF. We then review the therapeutic options for CCHF that have been investigated in human cases, followed by investigational drugs that have been evaluated in pre-clinical studies. We highlight the importance of understanding human prognostic factors in developing an animal model for CCHF that recapitulates hallmarks of human disease and its implication for selecting therapeutic candidates.

Pre-clinical development of a vaccine against Lassa fever.

Lassa virus (LASV) is a persistent global health threat that causes about half a million cases of Lassa fever each year in Western Africa. Although most cases are mild, the disease can cause significant morbidity and results in as many as 5,000 deaths per year. Since 2015, Nigeria has been experiencing a severe and extended outbreak of Lassa fever, raising concerns that it could spill over into other countries and reach a magnitude similar to the West African Ebola outbreak of 2013-2016. Despite the burden that Lassa fever places on public health, both in Africa and around the world, there are still no clinically-approved therapeutics or vaccines to treat or prevent it. Nevertheless, a number of promising candidate vaccines have been developed over the last several years, and there is a growing political and social determination to drive at least one of these candidates towards licensure. This paper describes a LASV vaccine candidate that is being developed at Canada's National Microbiology Laboratory. Based on the same live attenuated vesicular stomatitis virus (VSV) vaccine platform that was used to produce the successful Ebola virus vaccine, the VSV-based LASV vaccine has been shown to elicit a potent and protective immune response against LASV. The vaccine shows 100% protection in the "gold-standard" nonhuman primate model of Lassa fever, inducing both humoral and cellular immune responses. Moreover, studies have shown that a single vaccination may offer universal protection against numerous different strains of the virus, and additional studies have shown that immunization with the VSV platform appears to be unaffected by pre-existing immunity to VSV. The next step in the development of the VSV-based LASV vaccine is phase I human clinical trials to assess vaccine safety and dosage.

Hantavirus pulmonary syndrome in Canada: An overview of clinical features, diagnostics, epidemiology and prevention.

Hantavirus pulmonary syndrome is a disease caused by the inhalation of excreta from infected deer mice. In Canada, the majority of hantavirus pulmonary syndrome cases occur in the western provinces of British Columbia, Alberta, Saskatchewan and Manitoba and the primary cause of the illness is the Sin Nombre virus. Only one case of hantavirus pulmonary syndrome has been documented in eastern Canada (Québec); however, Sin Nombre virus-infected deer mice have been identified across the country. Although cases are rare (yearly case numbers range from zero to 13 and the total number of confirmed cases in Canada now total 109), the mortality rate among infected individuals is approximately 30%. The majority of cases occur in the spring and early summer indicating seasonally-associated risk factors for viral exposure. In 2013 and 2014, a substantial increase in the number of hantavirus pulmonary syndrome cases was identified; however the cause remains unclear. No antivirals or vaccines are currently available and treatment is supportive. Public education, rodent control and the use of personal protective measures are key to avoid infections in at-risk populations.

Virology. Mutation rate and genotype variation of Ebola virus from Mali case sequences.

The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 × 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns.

Differentiation and quantitation of human herpesviruses 6A, 6B and 7 by real-time PCR.

The beta-herpesviruses cause considerable morbidity in immunocompromised individuals, such as transplant patients. Most notably within this group is human cytomegalovirus, although HHV-6 and -7 are a growing concern. Identifying HHV-6 and -7 as the cause of post-transplant illness can be challenging due to high seroprevalence and latency properties associated with these human herpesviruses. We have developed a sensitive and specific real-time PCR assay, which can differentiate reliably and quantify HHV-6A, -6B and -7. Using two sets of hybridization probes specific for HHV-6A or -6B and HHV-7, the assay reliably differentiates the three viruses using melting curve analysis. The lower limit of detection for all three viruses was determined to be ten viral genomes. This real-time PCR assay will be useful for differentiation and quantitation of HHV-6A, -6B and -7, especially for monitoring transplant patients.

Lassa fever in West Africa: evidence for an expanded region of endemicity.

Lassa virus (LASV) is endemic in Sierra Leone, Guinea and Liberia (known as the Mano River region) and Nigeria and Lassa fever cases from these countries are being reported annually. Recent investigations have found evidence for an expanded endemicity zone between the two known Lassa endemic regions indicating that LASV is more widely distributed throughout the Tropical Wooded Savanna ecozone in West Africa.

Mapping ganciclovir resistance in the human herpesvirus-6 U69 protein kinase.

Human herpesvirus-6 (HHV-6) is a growing concern in immunocompromised individuals, such as in the transplant setting. Alone, or in concert with human cytomegalovirus (HCMV), infections with HHV-6 are often severe enough to require antiviral therapy, generally in the form of ganciclovir (GCV). GCV resistance in HCMV is well documented, both clinically and in the laboratory, and has been shown to result from mutations in the UL97 protein kinase and/or UL54 DNA polymerase. GCV resistance in HHV-6 has been documented. However, to date, it has only been investigated to a limited extent. The baculovirus system has previously been shown to be useful in studying GCV resistance with respect to herpesvirus protein kinase mutations. Using the baculovirus system, we created recombinant baculoviruses expressing either a wild-type HHV-6 U69 protein kinase or a mutated form containing homologous mutations to those documented in the UL97 protein kinase of GCV resistant HCMV isolates. The recombinant baculoviruses were used to infect Sf-9 cells and cultured in the presence of GCV to determine the effect of the HHV-6 U69 protein kinase mutations on GCV susceptibility. Mutations in the HHV-6 U69 protein kinase, homologous to those in the HCMV UL97 protein kinase documented to cause GCV resistance, result in GCV resistance in the recombinant baculoviruses.