Yaniv Lustig

Detection of Zika virus RNA in whole blood of imported Zika virus disease cases up to 2 months after symptom onset, Israel, December 2015 to April 2016

Zika virus RNA presence in serum, whole-blood and urine samples from six Israeli travellers symptomatic for Zika virus disease was examined. Whole-blood samples were positive for as late as 2 months (58 days) post-symptom onset, longer than for urine (26 days) and serum (3 days). These findings suggest the utility of whole blood in Zika infection diagnosis.

RNA-Binding Protein PTB and MicroRNA-221 Coregulate AdipoR1 Translation and Adiponectin Signaling

Adiponectin receptor 1 (AdipoR1) mediates adiponectin’s pleiotropic effects in muscle and liver and plays an important role in the regulation of insulin resistance and diabetes. Here, we demonstrate a pivotal role for microRNA-221 (miR-221) and the RNA-binding protein polypyrimidine tract–binding protein (PTB) in posttranscriptional regulation of AdipoR1 during muscle differentiation and in obesity. RNA-immunoprecipitation and luciferase reporter assays illustrated that both PTB and miR-221 bind AdipoR1-3′UTR and cooperatively inhibit AdipoR1 translation. Depletion of PTB or miR-221 increased, while overexpression of these factors decreased, AdipoR1 protein synthesis in both muscle and liver cells. During myogenesis, downregulation of PTB and miR-221 robustly induced AdipoR1 translation, providing a mechanism for enhanced AdipoR1 protein expression and activation in differentiated muscle cells. In addition, since both PTB and miR-221 are upregulated in liver and muscle of genetic and dietary mouse models of obesity, this novel translational mechanism may be at least partly responsible for the reduction in AdipoR1 protein levels in obesity. These findings highlight the importance of translational control in regulating AdipoR1 protein expression and adiponectin signaling. Given that adiponectin is reduced in obesity, induction of AdipoR1 could potentially enhance adiponectin beneficial effects and ameliorate insulin resistance and diabetes.

The Clinical Spectrum of Zika Virus in Returning Travelers

INTRODUCTION The clinical spectrum of Zika virus had, to date, been described in small series from endemic/epidemic countries and is not well established. METHODS We describe the clinical manifestations of laboratory-proven Zika virus infection in Israeli travelers during December 2015-February 2016, and review all published cases of travel-related Zika virus. RESULTS During the study period, 8 returning Israeli travelers were diagnosed with Zika virus infection. In addition, 41 published cases were included, mostly from Latin America to Europe and North America. Overall, 65.3% were diagnosed by polymerase chain reaction. Rash was the most frequent symptom, present in 95.7% of cases, followed by fever and arthralgia. Conjunctivitis was present in 53.1%; however, only 40.3% presented with a triad of conjunctivitis, fever, and rash. Less frequent symptoms included dysgeusia and nightmares, which, together with arthralgia, persisted for several weeks in some travelers. CONCLUSIONS Zika virus clinical picture in travelers is diverse. Prolonged symptoms may occur.

Zika Virus Disease in Traveler Returning from Vietnam to Israel.

To the Editor: On February 1, 2016, the World Health Organization designated the Zika virus disease outbreak in Latin America as a Public Health Emergency of International Concern (1). Genetic and epidemiological data suggest that Zika virus had been present in Southeast Asia since the 1940s (2); however, the disease burden and geographic extent of Zika virus disease in Asia are not clear. Occasional cases in some Asian countries, mostly in returning travelers, have recently been documented (3–5); however, as of February 2016, none were in Vietnam.

Sensitivity and Kinetics of an NS1-Based Zika Virus Enzyme-Linked Immunosorbent Assay in Zika Virus-Infected Travelers from Israel, the Czech Republic, Italy, Belgium, Germany, and Chile

ABSTRACT Serological diagnosis of Zika virus is challenging due to high cross-reactivity of Zika virus with other flavivirus antibodies. Recently, a Zika NS1-based enzyme-linked immunosorbent assay (ELISA) was developed and shown to be highly specific for Zika antibody detection; however, sensitivity was evaluated for only a small number of confirmed Zika-infected patients. In this study, we measured the sensitivity and kinetics of Zika IgM and IgG antibodies using the Zika NS1-based ELISA in 105 samples from 63 returning travelers infected with Zika virus (proven by PCR or neutralization assay) from Israel, Czech Republic, Italy, Belgium, Germany, and Chile. Zika virus IgM was detected from 2 to 42 days post-symptom onset (PSO) with an overall sensitivity of 79% in the first month and 68% until 2 months PSO, while IgG antibodies were detected from 5 days to 3 years PSO with 79% sensitivity. Interestingly, significant differences in IgM sensitivity and IgM detection period were observed between Israeli and European/Chilean Zika-infected travelers, adding to the complexity of Zika infection diagnosis and suggesting that other diagnostic methods should be complemented to reduce false-negative results.

Superiority of West Nile Virus RNA Detection in Whole Blood for Diagnosis of Acute Infection

ABSTRACT The current diagnosis of West Nile virus (WNV) infection is primarily based on serology, since molecular identification of WNV RNA is unreliable due to the short viremia and absence of detectable virus in cerebrospinal fluid (CSF). Recent studies have shown that WNV RNA can be detected in urine for a longer period and at higher concentrations than in plasma. In this study, we examined the presence of WNV RNA in serum, plasma, whole-blood, CSF, and urine samples obtained from patients diagnosed with acute WNV infection during an outbreak which occurred in Israel in 2015. Our results demonstrate that 33 of 38 WNV patients had detectable WNV RNA in whole blood at the time of diagnosis, a higher rate than in any of the other sample types tested. Overall, whole blood was superior to all other samples, with 86.8% sensitivity, 100% specificity, 100% positive predictive value, and 83.9% negative predictive value. Interestingly, WNV viral load in urine was higher than in whole blood, CSF, serum, and plasma despite the lower sensitivity than that of whole blood. This study establishes the utility of whole blood in the routine diagnosis of acute WNV infection and suggests that it may provide the highest sensitivity for WNV RNA detection in suspected cases.

Mosquito Surveillance for 15 Years Reveals High Genetic Diversity Among West Nile Viruses in Israel

West Nile Virus (WNV) is endemic in Israel and has been the cause of several outbreaks in recent years. In 2000, a countrywide mosquito survey was established to monitor WNV activity and characterize viral genotypes in Israel. We analyzed data from 7135 pools containing 277 186 mosquitoes collected over the past 15 years and, here, report partial sequences of WNV genomes obtained from 102 of the 336 positive mosquito pools. Phylogenetic analysis demonstrated that cluster 4 and the Mediterranean and Eastern European subtypes of cluster 2 within WNV lineage 1 circulated in Israel, as did WNV lineage 2, highlighting a high genetic diversity of WNV genotypes in our region. As a major crossroads for bird migration between Africa and Eurasia and with a long history of human infection, Israel serves as a resource hub for WNV in Africa and Eurasia and provides valuable information on WNV circulation in these regions.

Regulation and Function of Adiponectin Receptors in Skeletal Muscle

Obesity-induced insulin resistance is a primary contributing factor in the pathogenesis of type 2 diabetes. Adiponectin, an adipocyte-derived abundant plasma protein, has profound effects on systemic insulin sensitivity through direct action of the hormone on liver and muscle. The biological responses to adiponectin are mediated by two distinct receptors, AdipoR1 and AdipoR2, which differ in their affinities for adiponectin isoforms and exhibit cell type-specific effects. Disruption of AdipoR1 expression in muscle revealed a pivotal role of adiponectin/AdipoR1 in the regulation of mitochondrial biogenesis and insulin resistance. Here, we review the recent progress regarding adiponectin/AdipoRs signaling and function in skeletal muscle and summarize a range of physiological and pathophysiological conditions, as well as transcriptional and posttranscriptional mechanisms, controlling muscle AdipoR1 mRNA, and protein levels. Comprehensive understanding of the pathways that regulate AdipoRs expression in muscle is critical to benefit from the full therapeutic potential of the adiponectin-AdipoR system.

Francisella like endosymbionts and Rickettsia species in local and imported Hyalomma ticks.

ABSTRACT Hyalomma ticks (Acari: Ixodidae) are hosts for Francisella-like endosymbionts (FLE) and may serve as vectors of zoonotic disease agents. This study aimed to provide an initial characterization of the interaction between Hyalomma and FLE and to determine the prevalence of pathogenic Rickettsia in these ticks. Hyalomma marginatum, Hyalomma rufipes, Hyalommadromedarii, Hyalommaaegyptium, and Hyalommaexcavatum ticks, identified morphologically and molecularly, were collected from different hosts and locations representing the distribution of the genus Hyalomma in Israel, as well as from migratory birds. A high prevalence of FLE was found in all Hyalomma species (90.6%), as well as efficient maternal transmission of FLE (91.8%), and the localization of FLE in Malpighian tubules, ovaries, and salivary glands in H. marginatum. Furthermore, we demonstrated strong cophylogeny between FLE and their host species. Contrary to FLE, the prevalence of Rickettsia ranged from 2.4% to 81.3% and was significantly different between Hyalomma species, with a higher prevalence in ticks collected from migratory birds. Using ompA gene sequences, most of the Rickettsia spp. were similar to Rickettsiaaeschlimannii, while a few were similar to Rickettsiaafricae of the spotted fever group (SFG). Given their zoonotic importance, 249 ticks were tested for Crimean Congo hemorrhagic fever virus infection, and all were negative. The results imply that Hyalomma and FLE have obligatory symbiotic interactions, indicating a potential SFG Rickettsia zoonosis risk. A further understanding of the possible influence of FLE on Hyalomma development, as well as on its infection with Rickettsia pathogens, may lead to novel ways to control tick-borne zoonoses. IMPORTANCE This study shows that Francisella-like endosymbionts were ubiquitous in Hyalomma, were maternally transmitted, and cospeciated with their hosts. These findings imply that the interaction between FLE and Hyalomma is of an obligatory nature. It provides an example of an integrative taxonomy approach to simply differentiate among species infesting the same host and to identify nymphal and larval stages to be used in further studies. In addition, it shows the potential of imported Hyalomma ticks to serve as a vector for spotted fever group rickettsiae. The information gathered in this study can be further implemented in the development of symbiont-based disease control strategies for the benefit of human health.

Spatial distribution of West Nile virus in humans and mosquitoes in Israel, 2000–2014

OBJECTIVES Israel has a long history of West Nile virus (WNV) morbidity, and the rate of detection of WNV in mosquitoes has been high since 2000. The aim of this study was to integrate several WNV datasets in order to gain an insight into the geographical distribution of WNV in Israel. METHODS Three choropleth maps were generated showing WNV human morbidity, WNV prevalence in mosquitoes, and the results of a nationwide serological survey, based on the division of Israel into 15 sub-districts. RESULTS The maps show a high endemicity of WNV in Israel. In respect to the morbidity map, the population residing in the central part of the country and in Arava Region is at higher risk of developing the disease than the population of the rest of Israel. Interestingly, high prevalence rates of both WNV serology and WNV-infected mosquitoes were detected in Arava Region, but lower prevalence rates were detected in most areas of the coastal region, suggesting that other factors might also be important in the development of symptomatic WNV infections. CONCLUSIONS These results underline the high prevalence of WNV in Israel and point to specific risk areas for WNV infections across the country.