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  • 1
    Online Resource
    Online Resource
    The Rise and Fall of a Local SARS-CoV-2 Variant with the Spike Protein Mutation L452R
    MDPI AG ; 2021
    In:  Vaccines Vol. 9, No. 8 ( 2021-08-23), p. 937-
    Details
    In: Vaccines, MDPI AG, Vol. 9, No. 8 ( 2021-08-23), p. 937-
    Abstract: Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines9080937
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 2
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    HBV-RNA, Quantitative HBsAg, Levels of HBV in Peripheral Lymphocytes and HBV Mutation Profiles in Chronic Hepatitis B
    MDPI AG ; 2022
    In:  Viruses Vol. 14, No. 3 ( 2022-03-11), p. 584-
    Details
    In: Viruses, MDPI AG, Vol. 14, No. 3 ( 2022-03-11), p. 584-
    Abstract: A comprehensive characterization of chronic HBV (CHB) patients is required to guide therapeutic decisions. The cumulative impact of classical and novel biomarkers on the clinical categorization of these patients has not been rigorously assessed. We determined plasma HBV-RNA and HBsAg levels, HBV in peripheral lymphocytes (PBMCs) and HBV mutation profiles in CHB patients. Patient demographics (n = 139) and classical HBV biomarkers were determined during a clinical routine. HBV-RNA in plasma and HBV-DNA in PBMCs were determined by RT-PCR. HBsAg levels were determined using Architect. In samples with HBV-DNA viral load 〉 1000 IU/mL, genotype mutations in precore (PC), basal core promoter (BCP), HBsAg and Pol regions were determined by sequencing. Most patients (n = 126) were HBeAg-negative (HBeAgNeg) with significantly lower levels of HBV-RNA, HBV-DNA and HBsAg compared to HBeAg-positive (HBeAgPos) patients (p 〈 0.05). HBV genotype D prevailed (61/68), and 〉 95% had BCP/PC mutations. Escape mutations were identified in 22.6% (13/63). HBeAgNeg patients with low levels of HBsAg (log IU ≤ 3) were older and were characterized by undetectable plasma HBV-DNA and undetectable HBV-RNA but not undetectable HBV-DNA in PBMCs compared to those with high HBsAg levels. In 〉 50% of the studied HBeAgNeg patients (66/126), the quantitation of HBsAg and HBV-RNA may impact clinical decisions. In conclusion, the combined assessment of classical and novel serum biomarkers, especially in HBeAgNeg patients, which is the largest group of CHB patients in many regions, may assist in clinical decisions. Prospective studies are required to determine the real-time additive clinical advantage of these biomarkers.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14030584
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2516098-9
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  • 3
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    HIV-1 Circulating Recombinant Forms (CRFs) and Unique Recombinant Forms (URFs) in Israel, 2010–2018
    MDPI AG ; 2022
    In:  Viruses Vol. 14, No. 9 ( 2022-09-06), p. 1970-
    Details
    In: Viruses, MDPI AG, Vol. 14, No. 9 ( 2022-09-06), p. 1970-
    Abstract: Monitoring HIV-1 circulating recombinant forms (CRFs) and unique recombinant forms (URFs) is important for disease surveillance. Recombination may affect prevention efforts and interfere with the diagnosis and treatment of HIV-1 infection. Here, we characterized the epidemiology of HIV-1 CRFs and URFs in Israel. Partial pol sequences from treatment naïve patients diagnosed in 2010–2018 were assessed using the recombinant identification program (RIP), the recombinant detection program (RDP5), and using the maximum-likelihood phylogenetic method, using 410 reference sequences obtained from the Los Alamos database. CRFs and URFs were identified in 11% (213/1940) of all sequenced cases. The median age at diagnosis was 38 (30–47) years, 61% originated from Israel, and 82% were male. The most common were CRF02_AG (30.5%), CRF01_AE (16.9%), and the more complex forms CRF01_AE/CRF02_AG/A3 (10.8%) and B/F1 (7%). A significant increase in their overall proportion was observed in recent years (8.1% in 2010–2012, 20.3% in 2016–2018, p 〈 0.001). This increase was most prominent in individuals carrying CRF02_AG (2.5% in 2010–2015, 9.8% in 2016–2018, p 〈 0.001). Men who have sex with men (MSM) was the most common risk group; however, those infected with the secondary recombinant CRF02_AG/A6 were mainly injecting drug users (IDUs). The most common resistance mutations were K103N (5/213, 2.3%) and E138A (18/213, 8.5%) in the reverse transcriptase. Only E138A was more frequent in the recombinants compared with the classic subtypes and was significantly associated with a specific secondary CRF, CRF02_AG/A4. We concluded that CRFs and URFs were mainly detected in Israeli-born MSM and that an increase in the overall proportion of such HIV-1 sequences could be observed in more recent years.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14091970
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 4
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    Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients
    MDPI AG ; 2023
    In:  Viruses Vol. 15, No. 1 ( 2023-01-16), p. 253-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 1 ( 2023-01-16), p. 253-
    Abstract: The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers 〉 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25–82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p 〈 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin 〉 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p 〈 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15010253
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 5
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    Identification of Hepatitis E Virus Genotypes 3 and 7 in Israel: A Public Health Concern?
    MDPI AG ; 2021
    In:  Viruses Vol. 13, No. 11 ( 2021-11-22), p. 2326-
    Details
    In: Viruses, MDPI AG, Vol. 13, No. 11 ( 2021-11-22), p. 2326-
    Abstract: Background: Hepatitis E (HEV) is an emerging cause of viral hepatitis worldwide. Swine carrying hepatitis E genotype 3 (HEV-3) are responsible for the majority of chronic viral hepatitis cases in developed countries. Recently, genotype 7 (HEV-7), isolated from a dromedary camel in the United Arab Emirates, was also associated with chronic viral hepatitis in a transplant recipient. In Israel, chronic HEV infection has not yet been reported, although HEV seroprevalence in humans is ~10%. Camels and swine are 〉 65% seropositive. Here we report on the isolation and characterization of HEV from local camels and swine. Methods: Sera from camels (n = 142), feces from swine (n = 18) and blood from patients suspected of hepatitis E (n = 101) were collected during 2017–2020 and used to detect and characterize HEV sequences. Results: HEV-3 isolated from local swine and the camel-derived HEV-7 sequence were highly similar to HEV-3f and HEV-7 sequences (88.2% and 86.4%, respectively) related to viral hepatitis. The deduced amino acid sequences of both isolates were also highly conserved ( 〉 98%). Two patients were HEV-RNA positive; acute HEV-1 infection could be confirmed in one of them. Discussion: The absence of any reported HEV-3 and HEV-7 infection in humans remains puzzling, especially considering the reported seroprevalence rates, the similarity between HEV sequences related to chronic hepatitis and the HEV genotypes identified in swine and camels in Israel.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v13112326
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 6
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    Presence of Antibodies against Sindbis Virus in the Israeli Population: A Nationwide Cross-Sectional Study
    MDPI AG ; 2019
    In:  Viruses Vol. 11, No. 6 ( 2019-06-11), p. 542-
    Details
    In: Viruses, MDPI AG, Vol. 11, No. 6 ( 2019-06-11), p. 542-
    Abstract: Sindbis virus (SINV) is a mosquito-borne alphavirus circulating globally. SINV outbreaks have been mainly reported in North-European countries. In Israel, SINV was detected in 6.3% of mosquito pools; however, SINV infection in humans has rarely been diagnosed. A serologic survey to detect SINV IgG antibodies was conducted to evaluate the seroprevalence of SINV in the Israeli population. In total, 3145 serum samples collected in 2011–2014, representing all age and population groups in Israel, were assessed using an indirect ELISA assay, and a neutralization assay was performed on all ELISA-positive samples. The prevalence rates of SINV IgG antibodies were calculated. Logistic regressions models were applied to assess the association between demographic characteristics and SINV seropositivity. Overall, 113 (3.6%) and 59 (1.9%) samples were positive for ELISA and neutralization SINV IgG, respectively. Multivariable analysis demonstrated that SINV seropositivity was significantly associated with older age and residence outside metropolitan areas. These results demonstrate that, despite no outbreaks or clinical presentation, SINV infects the human population in Israel. Seropositivity is countrywide, more frequent in people of older age, and less diffuse in Israel’s metropolitan areas. Seroprevalence studies from other countries will add to our understanding of the global burden of SINV and the risk for potential SINV outbreaks.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v11060542
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
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  • 7
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    National Scale Real-Time Surveillance of SARS-CoV-2 Variants Dynamics by Wastewater Monitoring in Israel
    MDPI AG ; 2022
    In:  Viruses Vol. 14, No. 6 ( 2022-06-06), p. 1229-
    Details
    In: Viruses, MDPI AG, Vol. 14, No. 6 ( 2022-06-06), p. 1229-
    Abstract: In this report, we describe a national-scale monitoring of the SARS-CoV-2 (SC-2) variant dynamics in Israel, using multiple-time sampling of 13 wastewater treatment plants. We used a combination of inclusive and selective quantitative PCR assays that specifically identify variants A19/A20 or B.1.1.7 and tested each sample for the presence and relative viral RNA load of each variant. We show that between December 2020 and March 2021, a complete shift in the SC-2 variant circulation was observed, where the B.1.1.7 replaced the A19 in all examined test points. We further show that the normalized viral load (NVL) values and the average new cases per week reached a peak in January 2021 and then decreased gradually in almost all test points, in parallel with the progression of the national vaccination campaign, during February–March 2021. This study demonstrates the importance of monitoring SC-2 variant by using a combination of inclusive and selective PCR tests on a national scale through wastewater sampling, which is far more amendable for high-throughput monitoring compared with sequencing. This approach may be useful for real-time dynamics surveillance of current and future variants, such as the Omicron (BA.1, BA.2) and other variants.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14061229
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 8
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    High Immune Response Rate to the Fourth Boost of the BNT162b2 Vaccine against the Omicron Variants of Concern among Liver Transplant Recipients
    MDPI AG ; 2022
    In:  Viruses Vol. 14, No. 12 ( 2022-12-12), p. 2769-
    Details
    In: Viruses, MDPI AG, Vol. 14, No. 12 ( 2022-12-12), p. 2769-
    Abstract: The immune response of liver transplant (LT) recipients to a third dose of the BNT162b2 mRNA vaccine significantly waned after four months. We aimed to evaluate the immune response and breakthrough infection rates of a fourth dose against the Omicron variants among LT recipients. LT recipients who had no past or active SARS-CoV-2 infection and received three doses of the BNT162b2mRNA vaccine were included. Of the 73 LT recipients, 50 (68.5%) received a fourth dose. The fourth dose was associated with a significantly higher positive immune response than the third dose. Receptor-binding domain (RBD) IgG and Omicron BA.1 and BA.2 neutralizing antibodies were determined at a median of 132 and 29 days after the third and fourth vaccines. They were 345 binding antibody units per milliliter (BAU/mL) vs. 2118 BAU/mL (p 〈 0.0001), 10 vs. 87 (p 〈 0.0001), and 15 vs. 149 (p = 0.001), respectively. Breakthrough infections were documented among nine (18%) LT recipients after the fourth dose and among seven (30.4%) patients following the third dose (p = 0.2); 93.5% of breakthrough infections were mild. The infection rate after the fourth dose was higher among diabetic vs. nondiabetic recipients (33.3% vs. 6.9%, respectively; p = 0.02). Further studies are needed to evaluate additional factors influencing the breakthrough infection rate among LT recipients.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14122769
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 9
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    A Unique SARS-CoV-2 Spike Protein P681H Variant Detected in Israel
    MDPI AG ; 2021
    In:  Vaccines Vol. 9, No. 6 ( 2021-06-08), p. 616-
    Details
    In: Vaccines, MDPI AG, Vol. 9, No. 6 ( 2021-06-08), p. 616-
    Abstract: The routine detection, surveillance, and reporting of novel SARS-CoV-2 variants is crucial, as these threaten to hinder global vaccination efforts. Herein we report a novel local variant with a non-synonymous mutation in the spike (S) protein P681H. This local Israeli variant was not associated with a higher infection rate or higher prevalence. Furthermore, the local variant was successfully neutralized by sera from fully vaccinated individuals at a comparable level to the B.1.1.7 variant and an Israel wild-type strain. While it is not a variant of concern, routine monitoring by sequencing is still required.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines9060616
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2703319-3
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  • 10
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    Epidemiology and Transmitted HIV-1 Drug Resistance among Treatment-Naïve Individuals in Israel, 2010–2018
    MDPI AG ; 2021
    In:  Viruses Vol. 14, No. 1 ( 2021-12-31), p. 71-
    Details
    In: Viruses, MDPI AG, Vol. 14, No. 1 ( 2021-12-31), p. 71-
    Abstract: Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010–2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in 〉 50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many ( 〉 65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010–2018 (21.1% in 2010–2012; 16.8% in 2016–2018) whereas those from EEU/CA increased significantly (21% in 2010–2012; 27.8% in 2016–2018, p 〈 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis, 〈 50 years old, carrying A1, had the highest risk for having TDRM. In conclusion, an increase in immigrants from EEU/CA and a decrease in those from SSA characterized the HIV-1 epidemic in 2010–2018. Baseline resistance testing should still be recommended to identify TDRM, and improve surveillance and care.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14010071
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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