Paul Gottlieb

Paul Gottlieb
City College of New York | CCNY

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71
Publications
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Introduction
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Publications

Publications (71)
Article
Full-text available
This editorial describes the efforts to establish a genome packaging assay for the ϕ6 bacteriophage, which were performed in the laboratory of Leonard Mindich, Ph [...]
Article
Full-text available
Adenoviruses (AdVs) cause infections in humans that range from mild to severe, and can cause outbreaks particularly in close contact settings. Several human AdV types have been identified, which can cause a wide array of clinical manifestations. AdV types 4 and 7 (AdV-4 and AdV-7), which are among the most commonly circulating types in the United S...
Article
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The year 2023 marks the fiftieth anniversary of the discovery of the bacteriophage φ6. The review provides a look back on the initial discovery and classification of the lipid-containing and segmented double-stranded RNA (dsRNA) genome-containing bacteriophage—the first identified cystovirus. The historical discussion describes, for the most part,...
Article
Full-text available
Virus-like particles (VLPs) offer great potential as a safe and effective vaccine platform against SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 VLPs can be generated by expression of the four viral structural proteins in a mammalian expression system. Immunization of mice with a monovalent VLP vaccine elicited a potent...
Article
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Recombination and mutation of viral genomes represent major mechanisms for viral evolution and, in many cases, moderate pathogenicity. Segmented genome viruses frequently undergo reassortment of the genome via multiple infection of host organisms, with influenza and reoviruses being well-known examples. Specifically, major genomic shifts mediated b...
Article
Porcine circovirus 2 (PCV2) has a major impact on the swine industry. Eight PCV2 genotypes (a-h) have been identified using capsid sequence analysis. PCV2d has been designated as the emerging genotype. The cryo-electron microscopy molecular envelope of PCV2d virus-like particles identifies differences between PCV2a, b and d genotypes that accompany...
Preprint
Full-text available
Porcine circovirus 2 ( PCV2 ) is a T=1 non-enveloped icosahedral virus that has a major impact on the swine industry as an agent of porcine circovirus associate disease. PCV2 capsid protein sequences have been employed by others to provide a temporal description of the emerging genotypes. PCV2a is believed to be the earliest genotype and responsibl...
Article
Four sediments in the colloidal size range: goethite, montmorillonite, illite, and kaolinite, were suspended with the bacteriophage φ6, a model enveloped virus, to determine relative rates of heteroaggregation and the effect of aggregation on virus viability. Turbidity was measured on combinations of virus and each sediment type at low concentratio...
Article
Full-text available
The 3-dimensional structure of the nucleocapsid (NC) of bacteriophage φ6 is described utilizing component tree analysis, a topological and geometric image descriptor. The component trees are derived from density maps of cryo-electron microscopy single particle reconstructions. Analysis determines position and occupancy of structure elements respons...
Article
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The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and e...
Article
Full-text available
Respiratory Syncytial Virus (RSV) is the leading cause of severe respiratory disease in infants and children and represents an important health burden for the elderly and the immunocompromised globally. In spite of decades of research efforts, no licensed vaccine is available for RSV. We have developed virus-like particle (VLP) based RSV vaccines a...
Article
The interaction between influenza virus [subtype A/Puerto Rico/8/1934 H1N1, (PR8)] and montmorillonite (Mt) is investigated by transmission electron microscopy and biochemical methods to determine how PR8 morphology and viability is affected. The majority of the PR8 particles formed aggregates with the Mt. TEM analysis showed that the virus particl...
Article
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Protein P7 is a component of the cystovirus viral polymerase complex. In the unpackaged procapsid, the protein is situated in close proximity to the viral directed RNA polymerase, P2. Cryo-electron microscopy difference maps from the species φ6 procapsid have demonstrated that P7 and P2 likely interact prior to viral RNA packaging. The location of...
Chapter
Influenza is a rapidly changing virus that appears seasonally in the human population. Every year a new strain of the influenza virus appears with the potential to cause a serious global pandemic. Knowledge of the structure and density of the surface proteins is of critical importance in a vaccine candidate. Reconstruction techniques from a series...
Conference Paper
Full-text available
An understanding of the three-dimensional structure of a biological macromolecular complex is essential to fully understand its function. A component tree is a topological and geometric image descriptor that captures information regarding the structure of an image based on the connected components determined by different grayness thresholds. We bel...
Article
Full-text available
Cryo-electron microscopy projection image analysis and tomography is used to describe the overall architecture of influenza B/Lee/40. Algebraic reconstruction techniques with utilization of volume elements (blobs) are employed to reconstruct tomograms of this pleomorphic virus and distinguish viral surface spikes. The purpose of this research is to...
Article
Full-text available
Prior studies of clay-virus interactions have focused on the stability and infectivity of nonenveloped viruses, yielding contradictory results. We hypothesize that the surface charge distribution of the clay and virus envelope dictates how the components react and affect aggregation, viral stability, and infectivity. The bacteriophage Cystoviridae...
Article
Critical-zone reactions involve inorganic and biogenic colloids in a cation-rich environment. The present research defines the rates and structure of purified Mg-montmorillonite aggregates formed in the presence of monovalent (K+) and divalent (Ca2+, Mg2+) cations using light-extinction measurements. Time evolution of turbidity was employed to dete...
Article
Full-text available
The objective of this study was to determine the location of protein P7, the RNA packaging factor, in the procapsid of the φ6 cystovirus. A comparison of cryo-electron microscopy high-resolution single particle reconstructions of the φ6 complete unexpanded procapsid, the protein P2-minus procapsid (P2 is the RNA directed RNA-polymerase), and the P7...
Data
Tomogram of P124, P7-minus particle. (AVI)
Data
Tomogram of P147, P2-minus particle. (AVI)
Data
Difference Map of P1247 minus P147. (AVI)
Data
Difference Map of P1247 minus P124. (AVI)
Data
3-D Isosurface rendering of P1247 showing locations of the four PC proteins. (AVI)
Data
Tomogram of P1247, the complete procapsid. (AVI)
Conference Paper
Full-text available
Aggregation rates and fractal dimension of montmorillonite clay suspensions for Ca2+, Mg2+ or K+ cation concentrations in the range of 0.2 to 800 mM was determined from light extinction measurements.
Article
The Stokes shift of tryptophan (Trp) fluorescence from layers of the lipid-containing bacteriophage φ6 is compared to determine the relative effect of the layers on virus hydrophobicity. In the inner most layer, the empty procapsid (PC) which contains 80-90% of the virion Trp residues, λ(max) = 339.8 nm. The PC emission is substantially more redshi...
Article
Fluorescence Stokes shift measurements of tryptophan in bacteriophage ϕ6 were used to determine solvent exposure. It is determined that the envelope proteins are in a more hydrophobic environment than internal proteins of the polymerase complex.
Conference Paper
Spectroscopy of avian influenza hemagglutinin reveals changes in peak position and emission intensity of tryptophan fluorescence upon exposure to an acidic environment. These are attributed to conformational changes induced by lower pH.
Article
Full-text available
Cryo-electron tomography and subtomogram averaging are utilized to determine that the bacteriophage ϕ12, a member of the Cystoviridae family, contains surface complexes that are toroidal in shape, are composed of six globular domains with six-fold symmetry, and have a discrete density connecting them to the virus membrane-envelope surface. The lack...
Article
Several studies have shown an association between Systemic Lupus Erythematosus (SLE) and the Epstein Barr Virus (EBV). Our laboratory recently demonstrated that BALB/c mice injected with the major EBV nuclear antigen, EBNA-1, developed antibodies to EBNA-1 that cross-react with double stranded DNA (dsDNA). We generated monoclonal antibodies (MAbs)...
Article
Full-text available
Several genetic and environmental factors have been linked to Systemic Lupus Erythematosus (SLE). One environmental trigger that has a strong association with SLE is the Epstein Barr Virus (EBV). Our laboratory previously demonstrated that BALB/c mice expressing the complete EBNA-1 protein can develop antibodies to double stranded DNA (dsDNA). The...
Article
Several genetic and environmental factors have been linked to Systemic Lupus Erythematosus (SLE). One environmental trigger that has a strong association with SLE is the Epstein Barr Virus (EBV). Our laboratory previously demonstrated that BALB/c mice expressing the EBNA-1 protein, developed antibodies to double stranded DNA (dsDNA). The present st...
Article
Full-text available
The characterization of the initial stages of complex aggregate flocculation is a central problem of colloidal science and environmental studies. A fast, white light scattering technique for monitoring aggregation kinetics is used to provide a unique probe of the changes that transpire during flocculation. The time evolution of an accreting smectit...
Article
Full-text available
Bacteria play an important role in determining the properties and behavior of clay minerals in natural environments and such interactions have great potential for creating stable biofilms and carbon storage sites in soils, but our knowledge of these interactions are far from complete. The purpose of this study was to understand better the effects o...
Article
Full-text available
Bacteriophage phi12 is a member of the Cystoviridae, a unique group of lipid containing membrane enveloped bacteriophages that infect the bacterial plant pathogen Pseudomonas syringae pv. phaseolicola. The genomes of the virus species contain three double-stranded (dsRNA) segments, and the virus capsid itself is organized in multiple protein shells...
Article
Cystoviruses are a class of enveloped double-stranded RNA viruses that use a multiprotein polymerase complex (PX) to replicate and transcribe the viral genome. Although the structures of the polymerase and ATPase components of the cystoviral PX are known and their functional behavior is understood to a large extent, no atomic-resolution structural...
Article
Bacteriophage phi 12 is a member of the Cystoviridae virus family and contains a genome consisting of three segments of double-stranded RNA (dsRNA). This virus family contains eight identified members, of which four have been classified in regard to their complete genomic sequence and encoded viral proteins. A phospholipid envelope that contains th...
Article
Full-text available
Native fluorescence spectroscopy was used for in situ investigations of two lipid-containing bacteriophages from the cystovirus family as well as their Pseudomonad host cells. Both the viruses φ6 and φ12 and their bacterial host proteins contain the amino acid tryptophan (trp), which is the predominant fluorophore in UV. Within proteins, trp's stru...
Article
Systemic Lupus Erythematosus (SLE) is characterized by the production of antibodies to nuclear antigens, in particular antibodies to double stranded DNA (dsDNA). The etiology of these autoantibodies is unknown but one theory suggests that viruses may play a role. One virus that has been shown to have an association with SLE is the Epstein Barr Viru...
Article
Full-text available
Native fluorescence spectroscopy was used for in situ investigations of two lipid-containing bacteriophages from the cystovirus family as well as their Pseudomonad host cells. Both the viruses phi6 and phi12 and their bacterial host proteins contain the amino acid tryptophan (trp), which is the predominant fluorophore in UV. Within proteins, trp's...
Article
Many viruses employ molecular motors to package their genomes into preformed empty capsids (procapsids). In dsRNA bacteriophages the packaging motor is a hexameric ATPase P4, which is an integral part of the multisubunit procapsid. Structural and biochemical studies revealed a plausible RNA-translocation mechanism for the isolated hexamer. However,...
Article
Full-text available
UV fluorescence and absorption spectroscopy from Bacillus subtilis spores detected proteins and dipicolinic acid (DPA) released into the supernatant after heat treatments ranging from 20° to 90 ° C . The protein and DPA concentration in the supernatant was greater with higher heat treatment temperatures, undergoing a substantial increase for T ≥ 6...
Article
Full-text available
Native fluorescence spectroscopy (NFS), primarily from tryptophan (trp), was used for in situ investigation of the virus-receptor attachment process in phi6, a lipid-containing bacteriophage from the Cystoviridae family. NFS allowed us to monitor the viral attachment directly to its receptor, which was isolated from the pseudomonad host. Immediatel...
Article
Fluorescence and absorption spectroscopy were performed on Bacillus subtilis spores which were heat treated at temperatures ranging from 20°C to 90°C. The tryptophan (trp) emission from the spore suspensions treated at temperatures greater than 60°C was shifted towards longer wavelength as compared to the spores which were heat treated at lower tem...
Article
Full-text available
Light transmission measurements in the wavelength range of 400 to 1000 nm were performed on Bacillus subtilis spores at periodic time intervals after heat-shock induced activation. The Gaussian ray approximation, using a concentric sphere model for the spore coat and spore core, was used to calculate the scattering cross-section of the spores. Anal...
Article
Full-text available
Light-extinction measurements in the wavelength range of 400 to 1000 nm are performed in situ on Bacillus subtilis endospores during heat-shock-induced activation. Simultaneous information on particle size and refractive indices during activation is calculated from the transmission spectra by use of the Gaussian ray approximation of anomalous diffr...
Article
Full-text available
Bacteriophage φ12 protein P7 is a structural component of the polymerase complex and ensures stable packaging of the genomic RNA. φ12 P7 has been cloned, purified and crystallized. Crystals belong to space group P3221, with unit-cell parameters a = 75.7, b = 75.7, c = 45.2 Å, α = 90, β = 90, γ = 120°, and diffract beyond 2.0 Å. Multiple anomalous d...
Article
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the production of anti-nuclear antibodies. The etiology of SLE is unknown, although several viruses including the Epstein-Barr virus (EBV) have been implicated. An increase in the frequency of EBV infection has been observed in SLE patients relative to normal indiv...
Article
The fluorescence spectra from Phi6 and Phi12 cystoviruses and their pseudomonad host were investigated. The predominant fluorophore in both the Phi6 and Phi12 viruses and pseudomonas syringae is tryptophan. The emission maxima of the virus emission was found to be at 330 nm, compared to an emission maxima from the bacteria, which typically varies b...
Article
Full-text available
The hexameric ATPase P4 from bacteriophage φ12 is responsible for packaging single-stranded genomic precursors into the viral procapsid. P4 was overexpressed in Escherichia coli and purified. Crystals of native and selenomethionine-derivatized P4 have been obtained that belong to space group I222, with half a hexamer in the asymmetric unit and unit...
Article
To continue the molecular characterization of RNA-dependent RNA polymerases of dsRNA bacteriophages (Cystoviridae), we purified and biochemically characterized the wild-type (wt) and a temperature-sensitive (ts) point mutant of the polymerase subunit (Pol) from bacteriophage phi12. Interestingly, initiation by both wt and the ts phi12 Pol was notab...
Article
Full-text available
The isolation of additional bacteriophages besides phi6 containing segmented double-stranded RNA genomes (dsRNA) has expanded the Cystoviridae family to nine members. Comparing the genomic sequences of these viruses has allowed evaluation of important genetic as well as structural motifs. These comparative studies are resulting in greater understan...
Article
The isolation of additional bacteriophages containing segmented double-stranded RNA genomes has expanded the Cystoviridae family to nine members. Comparing the genomic sequences of these viruses has allowed evaluation of important genetic as well as structural motifs. These comparative studies are resulting in greater understanding of viral evoluti...
Article
The purpose of the present study was to produce an influenza A H2N2 donor virus from which an attenuating PB2 gene bearing three discrete temperature sensitive (ts) mutations could be readily transferred to currently epidemic influenza A H1N1 and H3N2 viruses via genetic reassortment. An influenza A transfectant virus was first produced that contai...
Article
The use of phthalocyanines in conjunction with red light has been shown to inactivate model lipid-enveloped viruses in red cell concentrates. The ability of this treatment to inactivate multiple forms of human immunodeficiency virus (HIV) was evaluated in this study. The phthalocyanines used were aluminum phthalocyanine tetrasulfonate (AIPcS4) and...
Article
Inactivation of the blood-borne parasite Trypanosoma cruzi by UVA and 4′-aminomethyl-4,5′,8-trimethylpsor-alen (AMT) was studied in the blood components fresh frozen plasma (FFP) and platelet concentrate (PC). The AMT was utilized at a concentration of 50 μg/mL and the inactivation procedure included the flavonoid rutin (at 0.35 mM), a quencher of...
Article
Three phthalocyanine dyes HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4), HOSiPcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5) and aluminum tetrasulfophthalocyanine hydroxide (AlOHPcS4) were evaluated for their ability to inactivate the trypomastigote form of Trypanosoma cruzi in fresh frozen plasma (FFP) and red blood cell concentrates (RBCC). The compound Pc 4 was found...
Article
Full-text available
The use of solvent/detergent mixtures and various forms of heat treatment to inactivate viruses has become widespread in the preparation of blood derivatives. Because viruses that lack lipid envelopes and/or are heat resistant, eg, hepatitis A virus (HAV) or parvovirus B19 may be present, the use of two methods of virus elimination that operate by...
Article
Currently transfused cellular components of blood are not available in a sterile form and carry a small risk of transmitting viral and parasite diseases. Using phthalocyanines and red light, lipid enveloped viruses, e.g., HIV-1, can be inactivated in red blood cell concentrates (RBCC). Under conditions leading to virus sterilization the blood borne...
Article
Hybridization of cloned ribosomal sequences to EcoRI-restricted genomic deoxyribonucleic acids of eight species and strains of the genus Bacillus produced multiband patterns consistent with the presence of 9 to 11 operons per genome. The basic structure of the repeating ribosomal gene set is highly conserved with the exception of one internal EcoRI...
Article
Deletions and additions of rRNA gene sets in Bacillus subtilis were observed by Southern hybridizations using cloned radiolabeled rDNA sequences. Of the ten rRNA gene sets found in B. subtilis 168M or NCTC3610, one was deleted in strains possessing the leuB1, ilvC1, argA2 and pheA1 mutations. Among EcoRI restriction fragments of genomic DNA product...

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