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State-of-the-Art Virology Research in Israel

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 26219

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Dr. Amnon Hizi

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Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
Interests: HIV; retroviruses; retroviral enzymes; reverse transcriptase (RT); integrase (IN)

Special Issue Information

Dear Colleagues,

After the establishment of Israel in 1948, biological research was gradually established there, including virology, which was mostly applied and encompassed human and plant diseases.

The crucial event was, arguably, the establishment in 1955 of a special governmental laboratory for combating the poliomyelitis virus. Due to the spreading epidemic in Israel, this small laboratory, headed by Drs. Nathan Goldblum and Tamar Gotlieb-Stemasky, started to produce an antiviral vaccine, following the methodology for the first successful anti-poliomyelitis vaccine by Dr. J. Salk in the USA (using a formalin-fixed dead virus). Early in 1957, the new, effective, “homemade” vaccine was used to immunize more than 60,000 babies and children, gradually leading to the elimination of poliomyelitis from Israel. Amazingly, the newly established state was the third in the world (after the USA and Denmark) to overcome poliomyelitis through extensive immunization.

Later, Goldblum established the virology department at the Hebrew University in Jerusalem, and Gotlieb-Stemasky became the head of the governmental Central Virology Laboratory that succeeded the poliovirus laboratory (which is currently headed by Dr. Ella Mendelson and is the major epidemiological clinically-related virology laboratory in Israel). Another important event was the establishment in 1960 by Dr. Gad Loebenstein of a governmental plant virology laboratory.

Since then, almost every research university has opened virology research laboratories. Among the first outstanding virologists (in addition to those mentioned above), who paved the way and trained many virologists, were Yechiel Becker in Jerusalem, Ifa Keydar in Tel Aviv, and Ernest Winocour and Leo Sachs at the Weizmann Institute.

Unfortunately, even today, virologists comprise a minority among basic biomedical researchers. The current SARS-CoV-2 pandemic will hopefully help to change this situation and increase the awareness of the importance of viral research in Israel and other developed countries.

The aim of this Special Issue of Viruses is to allow insights into the current virological research in Israel.

I look forward to receiving your submissions for this Special Issue.

Dr. Amnon Hizi
Guest Editor

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Published Papers (9 papers)

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25 pages, 4521 KiB

Open AccessArticle

Lytic Reactivation of the Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Is Accompanied by Major Nucleolar Alterations

by Nofar Atari, K. Shanmugha Rajan, Vaibhav Chikne, Smadar Cohen-Chalamish, Tirza Doniger, Odelia Orbaum, Avi Jacob, Inna Kalt, Shulamit Michaeli and Ronit Sarid

Viruses 2022, 14(8), 1720; https://0-doi-org.brum.beds.ac.uk/10.3390/v14081720 - 04 Aug 2022

Cited by 4 | Viewed by 2010

Abstract

The nucleolus is a subnuclear compartment whose primary function is the biogenesis of ribosomal subunits. Certain viral infections affect the morphology and composition of the nucleolar compartment and influence ribosomal RNA (rRNA) transcription and maturation. However, no description of nucleolar morphology and function during infection with Kaposi’s sarcoma-associated herpesvirus (KSHV) is available to date. Using immunofluorescence microscopy, we documented extensive destruction of the nuclear and nucleolar architecture during the lytic reactivation of KSHV. This was manifested by the redistribution of key nucleolar proteins, including the rRNA transcription factor UBF. Distinct delocalization patterns were evident; certain nucleolar proteins remained together whereas others dissociated, implying that nucleolar proteins undergo nonrandom programmed dispersion. Significantly, the redistribution of UBF was dependent on viral DNA replication or late viral gene expression. No significant changes in pre-rRNA levels and no accumulation of pre-rRNA intermediates were found by RT-qPCR and Northern blot analysis. Furthermore, fluorescent in situ hybridization (FISH), combined with immunofluorescence, revealed an overlap between Fibrillarin and internal transcribed spacer 1 (ITS1), which represents the primary product of the pre-rRNA, suggesting that the processing of rRNA proceeds during lytic reactivation. Finally, small changes in the levels of pseudouridylation (Ψ) and 2′-O-methylation (Nm) were documented across the rRNA; however, none were localized to the functional domain. Taken together, our results suggest that despite dramatic changes in the nucleolar organization, rRNA transcription and processing persist during lytic reactivation of KSHV. Whether the observed nucleolar alterations favor productive infection or signify cellular anti-viral responses remains to be determined. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Israel)

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16 pages, 5460 KiB

Open AccessArticle

Conformational Changes in Ff Phage Protein gVp upon Complexation with Its Viral Single-Stranded DNA Revealed Using Magic-Angle Spinning Solid-State NMR

by Smadar Kedem, Roni Rene Hassid, Yoav Shamir and Amir Goldbourt

Viruses 2022, 14(6), 1264; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061264 - 10 Jun 2022

Cited by 3 | Viewed by 1529

Abstract

Gene V protein (gVp) of the bacteriophages of the Ff family is a non-specific single-stranded DNA (ssDNA) binding protein. gVp binds to viral DNA during phage replication inside host Escherichia coli cells, thereby blocking further replication and signaling the assembly of new phage particles. gVp is a dimer in solution and in crystal form. A structural model of the complex between gVp and ssDNA was obtained via docking the free gVp to structures of short ssDNA segments and via the detection of residues involved in DNA binding in solution. Using solid-state NMR, we characterized structural features of the gVp in complex with full-length viral ssDNA. We show that gVp binds ssDNA with an average distance of 5.5 Å between the amino acid residues of the protein and the phosphate backbone of the DNA. Torsion angle predictions and chemical shift perturbations indicate that there were considerable structural changes throughout the protein upon complexation with ssDNA, with the most significant variations occurring at the ssDNA binding loop and the C-terminus. Our data suggests that the structure of gVp in complex with ssDNA differs significantly from the structure of gVp in the free form, presumably to allow for cooperative binding of dimers to form the filamentous phage particle. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Israel)

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15 pages, 1312 KiB

Open AccessArticle

National Scale Real-Time Surveillance of SARS-CoV-2 Variants Dynamics by Wastewater Monitoring in Israel

by Itay Bar-Or, Victoria Indenbaum, Merav Weil, Michal Elul, Nofar Levi, Irina Aguvaev, Zvi Cohen, Virginia Levy, Roberto Azar, Batya Mannasse, Rachel Shirazi, Efrat Bucris, Orna Mor, Alin Sela Brown, Danit Sofer, Neta S. Zuckerman, Ella Mendelson and Oran Erster

Viruses 2022, 14(6), 1229; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061229 - 06 Jun 2022

Cited by 5 | Viewed by 1713

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. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Israel)

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15 pages, 1330 KiB

Open AccessArticle

Functional Analysis of Spike from SARS-CoV-2 Variants Reveals the Role of Distinct Mutations in Neutralization Potential and Viral Infectivity

by Alona Kuzmina, Seraj Wattad, Stanislav Engel, Elli Rosenberg and Ran Taube

Viruses 2022, 14(4), 803; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040803 - 13 Apr 2022

Cited by 7 | Viewed by 1803

Abstract

Enhanced viral transmission and escape from vaccine–elicited neutralizing antibodies drive worldwide spread of SARS-CoV-2 variants and promote disease progression. However, the impact of specific spike mutations that are carried by different viral variants on viral infectivity and neutralization sensitivity has not been completely defined. Here, we use pseudoviruses to assess the contribution of spike mutations within the Receptor Binding Domain (RBD) and the Furin Cleavage Site (FCS), and appear in circulating viral variants, on viral infectivity and neutralization potential against sera that was drawn from fully vaccinated individuals. Our functional analysis demonstrates that single, P681H, P681R or A701V–FCS mutations do not play a role in viral infectivity and neutralization potential. However, when in conjunction with the RBD–N501Y mutation, viral infectivity is enhanced. Similarly, combining the E484K–RBD mutation to the spike that carries FCS mutations reduces neutralization sensitivity with no effects on viral infectivity. Employing a similar approach onto the spike from Delta or Lota SARS-CoV-2 variants further reveals that specific RBD mutations affect neutralization sensitivity or viral infectivity differently. Our results validate the efficacy of the Pfizer third dose vaccine against Delta and Lota SARS-CoV-2 variants, and outline the significance of distinct RBD mutations in promoting viral infectivity and neutralization sensitivity to post–vaccination sera. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Israel)

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11 pages, 842 KiB

Open AccessArticle

HBV-RNA, Quantitative HBsAg, Levels of HBV in Peripheral Lymphocytes and HBV Mutation Profiles in Chronic Hepatitis B

by Yael Gozlan, Daniella Aaron, Yana Davidov, Maria Likhter, Gil Ben Yakov, Oranit Cohen-Ezra, Orit Picard, Oran Erster, Ella Mendelson, Ziv Ben-Ari, Fadi Abu Baker and Orna Mor

Viruses 2022, 14(3), 584; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030584 - 11 Mar 2022

Cited by 2 | Viewed by 2918

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. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Israel)

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18 pages, 4161 KiB

Open AccessArticle

Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection

by Hadas Tamir, Sharon Melamed, Noam Erez, Boaz Politi, Yfat Yahalom-Ronen, Hagit Achdout, Shlomi Lazar, Hila Gutman, Roy Avraham, Shay Weiss, Nir Paran and Tomer Israely

Viruses 2022, 14(2), 189; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020189 - 19 Jan 2022

Cited by 14 | Viewed by 3227

Abstract

SARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA5 synthetic agonist Poly(I:C) against a lethal dose of SARS-CoV-2 in K18-hACE2 transgenic mice. We demonstrate here that early Poly(I:C) treatment acts synergistically with SARS-CoV-2 to induce an intense, immediate and transient upregulation of innate immunity-related genes in lungs. This effect is accompanied by viral load reduction, lung and brain cytokine storms prevention and increased levels of macrophages and NK cells, resulting in 83% mice survival, concomitantly with long-term immunization. Thus, priming the lung innate immunity by Poly(I:C) or alike may provide an immediate, efficient and safe protective measure against SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Israel)

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16 pages, 3001 KiB

Open AccessArticle

Modeling SARS-CoV-2 Infection in Mice Using Lentiviral hACE2 Vectors Infers Two Modes of Immune Responses to SARS-CoV-2 Infection

by Chaja Katzman, Tomer Israely, Sharon Melamed, Boaz Politi, Assa Sittner, Yfat Yahalom-Ronen, Shay Weiss, Reem Abu Rass, Rachel Zamostiano, Eran Bacharach, Marcelo Ehrlich, Nir Paran and Lior Nissim

Viruses 2022, 14(1), 11; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010011 - 21 Dec 2021

Viewed by 4504

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a severe global pandemic. Mice models are essential to investigate infection pathology, antiviral drugs, and vaccine development. However, wild-type mice lack the human angiotensin-converting enzyme 2 (hACE2) that mediates SARS-CoV-2 entry into human cells and consequently are not susceptible to SARS-CoV-2 infection. hACE2 transgenic mice could provide an efficient COVID-19 model, but are not always readily available, and practically restricted to specific strains. Therefore, there is a dearth of additional mouse models for SARS-CoV-2 infection. We applied lentiviral vectors to generate hACE2 expression in interferon receptor knock-out (IFNAR1^−/−) mice. Lenti-hACE2 transduction supported SARS-CoV-2 replication in vivo, simulating mild acute lung disease. Gene expression analysis revealed two modes of immune responses to SARS-CoV-2 infection: one in response to the exposure of mouse lungs to SARS-CoV-2 particles in the absence of productive viral replication, and the second in response to productive SARS-CoV-2 infection. Our results infer that immune response to immunogenic elements on incoming virus or in productively infected cells stimulate diverse immune effectors, even in absence of type I IFN signaling. Our findings should contribute to a better understanding of the immune response triggered by SARS-CoV-2 and to further elucidate COVID-19. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Israel)

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8 pages, 576 KiB

Open AccessArticle

Identification of Hepatitis E Virus Genotypes 3 and 7 in Israel: A Public Health Concern?

by Rachel Shirazi, Paolo Pozzi, Yael Gozlan, Marina Wax, Yaniv Lustig, Michal Linial, Ella Mendelson, Svetlana Bardenstein and Orna Mor

Viruses 2021, 13(11), 2326; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112326 - 22 Nov 2021

Cited by 4 | Viewed by 1838

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. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Israel)

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14 pages, 2831 KiB

Open AccessReview

Applications of Atomic Force Microscopy in HIV-1 Research

by Itay Rousso and Akshay Deshpande

Viruses 2022, 14(3), 648; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030648 - 21 Mar 2022

Cited by 5 | Viewed by 5386

Abstract

Obtaining an understanding of the mechanism underlying the interrelations between the structure and function of HIV-1 is of pivotal importance. In previous decades, this mechanism was addressed extensively in a variety of studies using conventional approaches. More recently, atomic force microscopy, which is a relatively new technique with unique capabilities, has been utilized to study HIV-1 biology. Atomic force microscopy can generate high-resolution images at the nanometer-scale and analyze the mechanical properties of individual HIV-1 virions, virus components (e.g., capsids), and infected live cells under near-physiological environments. This review describes the working principles and various imaging and analysis modes of atomic force microscopy, and elaborates on its distinctive contributions to HIV-1 research in areas such as mechanobiology and the physics of infection. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Israel)

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