TMPRSS2 is a functional receptor for human coronavirus HKU1.

Four endemic seasonal human coronaviruses causing common colds circulate worldwide: HKU1, 229E, NL63 and OC43 (ref. 1). After binding to cellular receptors, coronavirus spike proteins are primed for fusion by transmembrane serine protease 2 (TMPRSS2) or endosomal cathepsins2-9. NL63 uses angiotensin-converting enzyme 2 as a receptor10, whereas 229E uses human aminopeptidase-N11. HKU1 and OC43 spikes bind cells through 9-O-acetylated sialic acid, but their protein receptors remain unknown12. Here we show that TMPRSS2 is a functional receptor for HKU1. TMPRSS2 triggers HKU1 spike-mediated cell-cell fusion and pseudovirus infection. Catalytically inactive TMPRSS2 mutants do not cleave HKU1 spike but allow pseudovirus infection. Furthermore, TMPRSS2 binds with high affinity to the HKU1 receptor binding domain (Kd 334 and 137 nM for HKU1A and HKU1B genotypes) but not to SARS-CoV-2. Conserved amino acids in the HKU1 receptor binding domain are essential for binding to TMPRSS2 and pseudovirus infection. Newly designed anti-TMPRSS2 nanobodies potently inhibit HKU1 spike attachment to TMPRSS2, fusion and pseudovirus infection. The nanobodies also reduce infection of primary human bronchial cells by an authentic HKU1 virus. Our findings illustrate the various evolution strategies of coronaviruses, which use TMPRSS2 to either directly bind to target cells or prime their spike for membrane fusion and entry.

Chikungunya Outbreak in Country with Multiple Vectorborne Diseases, Djibouti, 2019-2020.

During 2019-2020, a chikungunya outbreak occurred in Djibouti City, Djibouti, while dengue virus and malaria parasites were cocirculating. We used blotting paper to detect arbovirus emergence and confirm that it is a robust method for detecting and monitoring arbovirus outbreaks remotely.

A novel SARS-CoV-2 related coronavirus in bats from Cambodia.

Knowledge of the origin and reservoir of the coronavirus responsible for the ongoing COVID-19 pandemic is still fragmentary. To date, the closest relatives to SARS-CoV-2 have been detected in Rhinolophus bats sampled in the Yunnan province, China. Here we describe the identification of SARS-CoV-2 related coronaviruses in two Rhinolophus shameli bats sampled in Cambodia in 2010. Metagenomic sequencing identifies nearly identical viruses sharing 92.6% nucleotide identity with SARS-CoV-2. Most genomic regions are closely related to SARS-CoV-2, with the exception of a region of the spike, which is not compatible with human ACE2-mediated entry. The discovery of these viruses in a bat species not found in China indicates that SARS-CoV-2 related viruses have a much wider geographic distribution than previously reported, and suggests that Southeast Asia represents a key area to consider for future surveillance for coronaviruses.

Genomic Epidemiology of 2015-2016 Zika Virus Outbreak in Cape Verde.

During 2015-2016, Cape Verde, an island nation off the coast of West Africa, experienced a Zika virus (ZIKV) outbreak involving 7,580 suspected Zika cases and 18 microcephaly cases. Analysis of the complete genomes of 3 ZIKV isolates from the outbreak indicated the strain was of the Asian (not African) lineage. The Cape Verde ZIKV sequences formed a distinct monophylogenetic group and possessed 1-2 (T659A, I756V) unique amino acid changes in the envelope protein. Phylogeographic and serologic evidence support earlier introduction of this lineage into Cape Verde, possibly from northeast Brazil, between June 2014 and August 2015, suggesting cryptic circulation of the virus before the initial wave of cases were detected in October 2015. These findings underscore the utility of genomic-scale epidemiology for outbreak investigations.

Drug Development against Smallpox: Present and Future.

Forty years after the last endemic smallpox case, variola virus (VARV) is still considered a major threat to humans due to its possible use as a bioterrorism agent. For many years, the risk of disease reemergence was thought to solely be through deliberate misuse of VARV strains kept in clandestine laboratories. However, recent experiments using synthetic biology have proven the feasibility of recreating a poxvirus de novo, implying that VARV could, in theory, be resurrected. Because of this new perspective, the WHO Advisory Committee on VARV Research released new recommendations concerning research on poxviruses that strongly encourages pursuing the development of new antiviral drugs against orthopoxviruses. In 2018, the U.S. FDA advised in favor of two molecules for smallpox treatment, tecovirimat and brincidofovir. This review highlights the difficulties to develop new drugs targeting an eradicated disease, especially as it requires working under the FDA "animal efficacy rule" with the few, and imperfect, animal models available.

Prevalence and risk factors for Extended-Spectrum Beta-Lactamase-producing- Enterobacteriaceae in French military and civilian travelers: A cross-sectional analysis.

BACKGROUND: International travel is a risk factor for colonization with Extended-Spectrum Beta-Lactamase-producing- Enterobacteriaceae (ESBL-E). We describe the prevalence of and risk-factors for ESBL-E colonization in civilian and military travelers. METHODS: Patients hospitalized in the infectious diseases department of Bégin Military Hospital (France) from May 2012 to November 2015, who had traveled abroad over the past two months, were screened for intestinal colonization with ESBL-E. RESULTS: Forty-one out of 166 travelers (24.7%) had ESBL-E colonization, predominantly Escherichia coli. The risk factors for ESBL-E colonization in the univariate analysis were a treatment with any antibiotic in the last two months (OR 4.19, 95% CI 1.91-9.16) or with a beta-lactam in the same period (OR 3.35, 95% CI 1.44-7.82), and an hospitalization in the last two months (OR 3.96, 95% CI 1.91-9.16). The military status, military mission or military accommodation were not associated with an increased risk of ESBL-E colonization. In the multivariate analysis, a treatment with any antibiotic in the last two months was significantly associated with ESBL-E colonization (OR 6.71, 95% CI 3.36-19.08). CONCLUSION: Antibiotic treatment in the two previous months is strongly predictive of ESBL-E colonization in international travelers, while the military status and its specific living conditions are not.

A World Health Organization Human Hepatitis E Virus Reference Strain Related to Similar Strains Isolated from Rabbits.

We report here the genome sequence of a hepatitis E virus (HEV) strain from a chronically infected immunodeficient patient. Full-length sequence analysis revealed a distinct HEV strain, of a tentative new subgenotype, clustering with viruses from rabbits. It is a World Health Organization reference strain for validation of nucleic acid testing.

Mycoplasma genitalium: a mycoplasma still underestimated.

Three men referred to the emergency department with suspected sexually transmitted infection like urethritis. After collection of several clinical specimens, they are sent home with a probabilistic treatment. Mycoplasma genitalium research is performed in first line, as Neisseria gonorrhoeae and Chlamydia trachomatis, and comes back positive. Patients are recalled in order to evaluate probabilistic treatment efficiency. M. genitalium, still underestimated because of its recent discovery, is responsible for 10 to 35% of non gonococcal acute and chronical urethritis. Its research is performed by PCR from urogenital specimens like genital swab or first void urine. Until recently, M. genitalium treatment included azithromycin 1g, antibiotic recommended in association with ceftriaxone in the probabilistic treatment of sexually transmitted infections. However, since the discovery of therapeutic failures and the emergence of resistance to azithromycin monodose, azithromycin in extended treatment (500 mg on the first day followed by 250 mg daily during 4 days) is now recommended as first-line agent when M. genitalium is well identified. A control by PCR is expected 4 or 5 weeks after treatment.

Coxsackievirus A24 Variant Associated with Acute Haemorrhagic Conjunctivitis Cases, French Guiana, 2017.

In 2017, numerous cases of acute haemorrhagic conjunctivitis (AHC) were reported in the Caribbean and in South America. Preliminary reports identified adenoviruses and enteroviruses in some patient samples but, until now, none of the etiologic agents have been fully characterized. We report the full-length genomic sequences of 4 coxsackievirus A24 (CV-A24) isolates collected from AHC patients in French Guiana during this outbreak (May and June 2017). These isolates are very closely related and belong to the genotype IV of CV-A24 variant, which consists of strains sampled worldwide during AHC outbreaks in the 2000s and 2010s. No recombination events were detected within the genomic sequences, indicating that members of this genotype have continuously circulated worldwide for more than 10 years without undergoing recombination with other enteroviruses. This unusual trait could be due to their ocular tropism that could impede genetic exchanges between these viruses and other enteroviruses, which replicate mainly in the gut.

The French Armed Forces Virology Unit: A Chronological Record of Ongoing Research on Orthopoxvirus.

Since the official declaration of smallpox eradication in 1980, the general population vaccination has ceased worldwide. Therefore, people under 40 year old are generally not vaccinated against smallpox and have no cross protection against orthopoxvirus infections. This naïve population may be exposed to natural or intentional orthopoxvirus emergences. The virology unit of the Institut de Recherche Biomédicale des Armées (France) has developed research programs on orthopoxviruses since 2000. Its missions were conceived to improve the diagnosis capabilities, to foster vaccine development, and to develop antivirals targeting specific viral proteins. The role of the virology unit was asserted in 2012 when the responsibility of the National Reference Center for the Orthopoxviruses was given to the unit. This article presents the evolution of the unit activity since 2000, and the past and current research focusing on orthopoxviruses.

Decontamination of a field laboratory dedicated to Ebola virus-infected patients.

In 2015, the French Armed Forces deployed a biosafety level 3 (BSL3) field laboratory as a part of an Ebola treatment center in Guinea. When closing the center, laboratory decontamination operations were necessary. We present the decontamination protocols applied for the BSL3 field laboratory, making the entire module ready for a future use.

Ebola Virus RNA Stability in Human Blood and Urine in West Africa's Environmental Conditions.

We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa's environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly.

Prevention of combat-related infections: antimicrobial therapy in battlefield and barrier measures in French military medical treatment facilities.

Infection is a major complication associated with combat-related injuries. Beside immobilization, wound irrigation, surgical debridement and delayed coverage, post-injury antimicrobials contribute to reduce combat-related infections, particularly those caused by bacteria of the early contamination flora. In modern warfare, bacteria involved in combat-related infections are mainly Gram-negative bacteria belonging to the late contamination flora. These bacteria are frequently resistant or multiresistant to antibiotics and spread through the deployed chain of care. This article exposes the principles of war wounds antimicrobial prophylaxis recommended in the French Armed Forces and highlights the need for high compliance to hygiene standard precautions, adapted contact precautions and judicious use of antibiotics in French deployed military medical treatment facilities (MTF).

[Update on Mycobacterium bovis infections in France: 4 cases reports]. / Actualités de l'infection à Mycobacterium bovis en France : à propos de 4 cas.

Mycobacterium bovis (M. bovis) is a cause of zoonosis. It is rare in developed countries since cattle control. We report four cases of M. bovis infection in people aged more 60 years. They were probably infected during infancy, consuming unpasteurized milk. It is the main transmission mode in developing countries where veterinary controls aren't made. M. bovis infections clinical aspects are varied and treatment is complicated by natural pyrazinamide resistance. Recent diagnostic methods using molecular biology are quick and specific and facilitate identification.