Z H Zhou

University of Texas Medical School, Houston, Texas, United States

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Publications (19)86.55 Total impact

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    ABSTRACT: Parvoviridae is a family of the smallest viruses known with a wide variety of hosts. The capsid structure of the Aedes albopictus C6/36 cell densovirus (C6/36 DNV) at 1.2-nm resolution was obtained by electron cryomicroscopy (cryoEM) and three-dimensional (3D) image reconstruction. Structure comparisons between the C6/36 DNV and other parvoviruses reveal that the degree of structural similarity between C6/36 DNV and the human parvovirus B19 is higher than that between C6/36 DNV and other insect parvoviruses. The amino acid sequence comparisons of structural and non-structural proteins also reveal higher levels of similarity between C6/36 DNV and parvovirus B19 than those between C6/36 DNV and other parvoviruses. These findings indicate that C6/36 DNV is closely related to the human virus B19, and the former might evolve from the human species other than from other insect viruses.
    Science in China Series C Life Sciences 03/2007; 50(1):70-4. · 1.61 Impact Factor
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    ABSTRACT: Grass carp reovirus (GCRV) is a relatively new virus first isolated in China and is a member of the Aquareovirus genus of the Reoviridae family. Recent report of genomic sequencing showed that GCRV shared high degree of homology with mammalian reovirus (MRV). As a step of our effort to understand the structural basis of GCRV pathogenesis, we determined the three-dimensional (3D) structure of GCRV capsid at 17 A resolution by electron cryomicroscopy. Each GCRV capsid has a multilayered organization, consisting of an RNA core, an inner, middle and outer protein layer. The outer layer is made up of 200 trimers that are arranged on an incomplete T=13 icosahedral lattice. A characteristic feature of this layer is the depression resulting from the absence of trimers around the peripentonal positions, revealing the underlying trimers on the middle layer. There are 120 subunits in the inner layer arranged with T=1 symmetry. These structural features are common to other members of the Reoviridae. Moreover, SDS-PAGE analysis showed that GCRV virions contain seven structural proteins (VP1-VP7). These structural proteins have a high degree of sequence homology to MRV, consistent with the structural similarities observed in our study. The high structural similarities of isolated GCRV and MRV suggest that future structural studies focusing on GCRV entering into and replicating within its host cell are necessary in order to fully understand the structural basis of GCRV pathogenesis.
    Science in China Series C Life Sciences 01/2006; 48(6):593-600. · 1.61 Impact Factor
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    ABSTRACT: The three-dimensional structure of capsid of Aedes albopictus C6/36 densovirus was determined to 14-A resolution by electron cryomicroscopy and computer reconstruction. The triangulation number of the capsid is 1. There are 12 holes in each triangular face and a spike on each 5-fold vertex. The validity of the capsid and nucleic acid densities in the reconstructions was discussed.
    Science in China Series C Life Sciences 07/2004; 47(3):224-8. · 1.61 Impact Factor
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    ABSTRACT: We report the isolation, sequencing, biochemical, and structural characterization of a previously undescribed virus in a chronically infected Aedes albopictus C6/36 cell line. This virus is identified as a new densovirus under the Densovirinae subfamily of the Parvoviridae based on its biological and morphologic properties as well as sequence homologies, and is tentatively designated A. albopictus C6/36 cell densovirus (C6/36 DNV). Analysis of the 4094 nt of the C6/36 DNV genome revealed that the plus strand had three large open reading frames (ORFs): a left ORF, a right ORF, and a mid-ORF (within the left ORF), whose potential coding capacities are 91.0, 40.8, and 41.2 kDa, respectively. The left ORF likely encodes the nonstructural protein NS-1, which contains NTP-binding and helicase domains. The right ORF likely encodes structural proteins, VP1 and VP2. Our analyses revealed that C6/36 DNV has a similar genomic organization and shares very high homology in nucleotide sequence and amino acid sequences with Aedes aegypti densovirus (AaeDNV) and A. albopictus densovirus (AalDNV), members of the genus Brevidensovirus of the Densovirinae. Similar to other densoviruses, C6/36 DNV has a different genomic organization and no recognizable sequence homology with viruses in the Parvovirinae. The three-dimensional (3D) reconstruction of the C6/36 DNV at 15.6-A resolution by electron cryomicroscopy (cryoEM) revealed distinctive outer surface features not previously seen in other parvoviruses, indicating structural divergence of densoviruses, in addition to its genomic differences, while the inner surface of the C6/36 DNV capsid exhibits features that are conserved among parvoviruses.
    Virology 02/2004; 318(1):123-33. · 3.37 Impact Factor
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    ABSTRACT: The RNA of Chinese Sacbrood Bee Virus (CSBV) was purified and used as template to obtain a 1096 bp cDNA fragment by RT-PCR amplification. This DNA fragment was cloned into pGEM-T Easy Vector for sequencing. Analyses of the sequenced CSBV RNA fragment revealed a nucleotide sequence homology of 87.6% and a deduced amino-acid sequence homology of 94.6% with that of the Sacbrood Virus (SBV), indicating that CSBV is a different but highly homologous virus of SBV. The three-dimensional (3D) structure of CSBV was determined at 2.5 nm resolution by using electron cryo-microscopy (cryoEM) and computer reconstruction methods. The 3-D structure showed that the capsid has aT = 1 (or P = 3) icosahedral capsid shell with a smooth surface. There were 12 pentons at its icosahedral vertices (5-fold axes) and 132 holes penetrating the shell. The 3-D structure also revealed densities corresponding to the CSBV genome, suggesting icosahedrally-ordered RNA organization, a novel feature not previously reported for any picornaviruses.
    Science in China Series C Life Sciences 09/2001; 44(4):443-8. · 1.61 Impact Factor
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    J He, M F Schmid, Z H Zhou, F Rixon, W Chiu
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    ABSTRACT: A characteristic of virus assembly is the use of symmetry to construct a complex capsid from a limited number of different proteins. Many spherical viruses display not only icosahedral symmetry, but also local symmetries, which further increase the redundancy of their structural proteins. We have developed a computational procedure for evaluating the quality of these local symmetries that allows us to probe the extent of local structural variations among subunits. This type of analysis can also provide orientation parameters for carrying out non-icosahedral averaging of quasi-equivalent subunits during three-dimensional structural determination. We have used this procedure to analyze the three types of hexon (P, E and C) in the 8.5 A resolution map of the herpes simplex virus type 1 (HSV-1) B capsid, determined by electron cryomicroscopy. The comparison of the three hexons showed that they have good overall 6-fold symmetry and are almost identical throughout most of their lengths. The largest difference among the three lies near the inner surface in a region of about 34 A in thickness. In this region, the P hexon displays slightly lower 6-fold symmetry than the C and E hexons. More detailed analysis showed that parts of two of the P hexon subunits are displaced counterclockwise with respect to their expected 6-fold positions. The most highly displaced subunit interacts with a subunit from an adjacent P hexon (P'). Using the local 6-fold symmetry axis of the P hexon as a rotation axis, we examined the geometrical relationships among the local symmetry axes of the surrounding capsomeres. Deviations from exact symmetry are also found among these local symmetry axes. The relevance of these findings to the process of capsid assembly is considered.
    Journal of Molecular Biology 07/2001; 309(4):903-14. · 3.91 Impact Factor
  • Science in China Series C-Life Sciences. 01/2001; 44.
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    ABSTRACT: Human herpesviruses are large and structurally complex viruses that cause a variety of diseases. The three-dimensional structure of the herpesvirus capsid has been determined at 8.5 angstrom resolution by electron cryomicroscopy. More than 30 putative alpha helices were identified in the four proteins that make up the 0.2 billion-dalton shell. Some of these helices are located at domains that undergo conformational changes during capsid assembly and DNA packaging. The unique spatial arrangement of the heterotrimer at the local threefold positions accounts for the asymmetric interactions with adjacent capsid components and the unusual co-dependent folding of its subunits.
    Science 06/2000; 288(5467):877-80. · 31.03 Impact Factor
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    ABSTRACT: Typical herpes simplex virus (HSV) capsids contain seven proteins that form a T=16 icosahedron of 1,250-A diameter. Infection of cells with recombinant baculoviruses expressing two of these proteins, VP5 (which forms the pentons and hexons in typical HSV capsids) and VP19C (a component of the triplexes that connect adjacent capsomeres), results in the formation of spherical particles of 880-A diameter. Electron cryomicroscopy and computer reconstruction revealed that these particles possess a T=7 icosahedral symmetry, having 12 pentons and 60 hexons. Among the characteristic structural features of the particle are the skewed appearance of the hexons and the presence of intercapsomeric mass densities connecting the middle domain of one hexon subunit to the lower domain of a subunit in the adjacent hexon. We interpret these connecting masses as being formed by VP19C. Comparison of the connecting masses with the triplexes, which occupy equivalent positions in the T=16 capsid, reveals the probable locations of the single VP19C and two VP23 molecules that make up the triplex. Their arrangement suggests that the two triplex proteins have different roles in controlling intercapsomeric interactions and capsid stability. The nature of these particles and of other aberrant forms made in the absence of scaffold demonstrates the conformational adaptability of the capsid proteins and illustrates how VP23 and the scaffolding protein modulate the nature of the VP5-VP19C network to ensure assembly of the functional T=16 capsid.
    Journal of Virology 09/1999; 73(8):6821-30. · 5.08 Impact Factor
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    ABSTRACT: Three-dimensional (3D) reconstruction from transmission electron cryomicroscopy images is a technique for 3D structure determination of macromolecular complexes such as spherical viruses with icosahedral symmetry. To calculate virus structures to higher resolution, it is necessary to combine information from hundreds (perhaps thousands) of high resolution but extremely noisy images. The most intensive step is an optimization calculation in which the parameters determining particle center and orientation are refined. The complexity increases quadratically as the number of particle images increases, making it impractical to refine hundreds of particles on conventional workstations. We discuss a parallel implementation of the refinement algorithm on shared-memory platforms. The speed-up obtained thus far has made it possible for us to reconstruct an improved resolution structure of herpes simplex virus-1 (HSV-1) capsid. 1 Introduction Three-dimensional structural determinatio...
    08/1999;
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    D H Chen, H Jiang, M Lee, F Liu, Z H Zhou
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    ABSTRACT: The three-dimensional structure of the intact human cytomegalovirus (HCMV) was determined to 18-A resolution by electron cryomicroscopy and computer reconstruction. Its capsid shell is composed of pentons, hexons, and triplexes arranged on a T = 16 icosahedral lattice and is identical to that of the B-capsid isolated from host cell nuclei. An icosahedrally ordered tegument layer formed by 960 copies of filamentous density is also visualized, which interacts with the pentons, hexons, and triplexes of the underlying capsid. The observed structural similarities and differences of HCMV with those of herpes simplex virus offer insights into the significance of the different tegument components for their infection processes while maintaining similar capsids.
    Virology 08/1999; 260(1):10-6. · 3.37 Impact Factor
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    ABSTRACT: Unlike the multiple-shelled organization of other Reoviridae members, cytoplasmic polyhedrosis virus (CPV) has a single-shelled capsid. The three-dimensional structures of full and empty CPV by electron cryomicroscopy show identical outer shells but differ inside. The outer surface reveals a T=1 icosahedral shell decorated with spikes at its icosahedral vertices. The internal space of the empty CPV is unoccupied except for 12 mushroom-shaped densities attributed to the transcriptional enzyme complexes. The ordered double-stranded RNA inside the full capsid forms spherical shells spaced 25 A apart. The RNA-protein interactions suggest a mechanism for RNA transcription and release.
    Journal of Virology 03/1999; 73(2):1624-9. · 5.08 Impact Factor
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    ABSTRACT: Rice dwarf virus (RDV), a member of the Reoviridae family, is a double-stranded RNA virus. Infection of rice plants with RDV reduces crop production significantly and can pose a major economic threat to Southeast Asia. A 25-A three-dimensional structure of the 700-A-diameter RDV capsid has been determined by 400-kV electron cryomicroscopy and computer reconstruction. The structure revealed two distinctive icosahedral shells: a T=13l outer icosahedral shell composed of 260 trimeric clusters of P8 (46 kDa) and an inner T=1 icosahedral shell of 60 dimers of P3 (114 kDa). Sequence and structural comparisons were made between the RDV outer shell trimer and the two crystal conformations (REF and HEX) of the VP7 trimer of bluetongue virus, an animal analog of RDV. The low-resolution structural match of the RDV outer shell trimer to the HEX conformation of VP7 trimer has led to the proposal that P8 consists of an upper domain of beta-sandwich motif and a lower domain of alpha helices. The less well fit REF conformation of VP7 to the RDV trimer may be due to the differences between VP7 and P8 in the sequence of the hinge region that connects the two domains. The additional mass density and the absence of a known signaling peptide on the surface of the RDV outer shell trimer may be responsible for the different interactions between plants and animal reoviruses.
    Journal of Virology 12/1998; 72(11):8541-9. · 5.08 Impact Factor
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    ABSTRACT: Formation of herpes simplex virus-1 capsids requires the presence of intact scaffolding proteins. The C terminus of the abundant scaffolding protein associates with the major capsid shell protein VP5 through hydrophobic interactions. After cleavage by the viral encoded protease, which removes their C-terminal 25 aa, the scaffolding proteins are released from the capsid. We have used electron cryomicroscopy and computer image processing to determine, to 13 A, the three-dimensional structures of capsids containing either cleaved or uncleaved scaffolding proteins. Detailed comparisons show that the structures of the outer icosahedral shells are almost identical in the two capsid types. Differences are apparent in the radial distribution of the density inside the capsid shell (within a radius of 460 ) which represents the scaffolding core. However, in both capsid types, the bulk of this internal density exhibits no icosahedral symmetry. Close examination revealed localized regions of icosahedrally arranged extra density at the interface between the outer shell and the scaffold of protease-minus capsids. Rod-like densities extending inwards for approximately 40 from the capsid shell are present under four of the six quasi-equivalent triplex positions. Under triplexes Tb, Tc, and Te, the major additional densities appear as pairs with the rods in each pair situated 37 apart. We propose that these rods are formed by the C-termini of the scaffolding proteins and represent the sites of interaction between the capsid shell and scaffold.
    Proceedings of the National Academy of Sciences 03/1998; 95(6):2778-83. · 9.81 Impact Factor
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    ABSTRACT: Electron cryomicroscopy and icosahedral reconstruction are used to obtain the three-dimensional structure of the 1250-A-diameter herpesvirus B-capsid. The centers and orientations of particles in focal pairs of 400-kV, spot-scan micrographs are determined and iteratively refined by common-lines-based local and global refinement procedures. We describe the rationale behind choosing shared-memory multiprocessor computers for executing the global refinement, which is the most computationally intensive step in the reconstruction procedure. This refinement has been implemented on three different shared-memory supercomputers. The speedup and efficiency are evaluated by using test data sets with different numbers of particles and processors. Using this parallel refinement program, we refine the herpesvirus B-capsid from 355-particle images to 13-A resolution. The map shows new structural features and interactions of the protein subunits in the three distinct morphological units: penton, hexon, and triplex of this T = 16 icosahedral particle.
    Biophysical Journal 02/1998; 74(1):576-88. · 3.67 Impact Factor
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    ABSTRACT: We implement a graphical user interface in an X-window/UNIX environment to compute and display the incoherently averaged Fourier transforms of electron images of single particles embedded in ice and the simulated contrast transfer function with or without envelope functions. This interface provides an easy and efficient operation for the determination of defocus value and the evaluation of the extent of Fourier amplitude falloff. This computational procedure is crucial for prescreening image data and performing image correction of contrast transfer function in high-resolution three-dimensional reconstruction of single particles.
    Journal of Structural Biology 01/1996; 116(1):216-22. · 3.36 Impact Factor
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    ABSTRACT: The 1250 A diameter herpes simplex virus-1 (HSV-1) capsid shell consists of four major structural proteins, of which VP26 (approximately 12,000 M(r)) is the smallest. Using 400 kV electron cryomicroscopy and computer reconstruction, we have determined the three-dimensional structures of the wild-type capsid and a recombinant baculovirus-generated HSV-1 capsid which lacks VP26. Their difference map demonstrates the presence of VP26 hexamers attached to all the hexons in the wild-type capsid, and reveals that the VP26 molecule consists of a large and a small domain. Although both hexons and pentons are predominantly composed of VP5, VP26 is not present on the penton. Based on the interactions involving VP26 and the hexon subunits, we propose a mechanism for VP26 assembly which would account for its distribution. Possible roles of VP26 in capsid stability and DNA packaging are discussed.
    Nature Structural Biology 12/1995; 2(11):1026-30.
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    ABSTRACT: The three-dimensional structure of the A-capsid of herpes simplex virus type-1 has been determined to a resolution of approximately 26 A by using 400 kV spot-scan electron cryomicroscopy and computer image reconstruction techniques. The density map of the capsid has revealed several new structural details in the protein subunits of pentons, hexons, and triplexes. Our structural analysis has provided further evidence for the assignment of the four major capsid proteins to these various subunits. VP5, a 150 kDa major capsid protein that makes up both the penton and the bulk of the hexon subunits, has three domains: an upper diamond-shaped domain, a middle stem-like domain, and a lower anchoring domain. Structural differences are noticeable between the VP5 subunits in various quasi-equivalent environments. A horn-shaped mass density present at the distal end of each hexon subunit but missing from the penton subunit has been assigned to VP26, a minor 12 kDa protein. The six types of triplexes have similar, but not identical, features that include two legs and an upper domain that has a tail, which are interpreted to be formed from two copies of VP23 (36 kDa) and one copy of VP19c (57 kDa), respectively. Each triplex has two arms that interact with the adjacent VP5 subunits, and the modes of interaction vary among the quasi-equivalent triplexes. The 25 A-thick floor of the capsid is formed by the close association of the lower domains of subunits from the hexons, pentons, and triplexes. The interior of the capsid is accessible through the trans-capsomeric channels and the holes at the base of each triplex. These openings may play a role in the transport of genomic DNA and scaffolding proteins during capsid morphogenesis.
    Journal of Molecular Biology 10/1994; 242(4):456-69. · 3.91 Impact Factor
  • Z H Zhou, W Chiu
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    ABSTRACT: Specimen preparation and imaging techniques for biological macromolecules have been improved to the point where attention to the electron-optical imaging conditions becomes a significant factor for achieving high resolution. A field emission gun (FEG) can provide an illumination source with a better spatial and temporal coherence suitable for imaging near atomic resolution. Our computational analysis of carbon film images taken between Scherzer focus and 1.1 microns underfocus (20x Scherzer focus) with the Hitachi 200 kV microscope with a cold field emission gun shows detectable contrast beyond 3.5 A resolution. In biological imaging, a large defocus is often used to optimize the low-resolution contrast in order to facilitate the subsequent steps in computer reconstruction. An intermediate-voltage electron microscope (IVEM) would optimize the contrast at high resolution by reducing the temporal coherent effects. In theory, the IVEM would give a greater depth of field so that large macromolecular assemblies such as viruses and cellular structures can be interpreted and reconstructed reliably using the projection approximation. These experimental and theoretical considerations provide a rationale for designing a future IVEM with a FEG suitable for biological macromolecule imaging close to atomic resolution.
    Ultramicroscopy 03/1993; 49(1-4):407-16. · 2.47 Impact Factor

Publication Stats

854 Citations
86.55 Total Impact Points

Institutions

  • 1998–2007
    • University of Texas Medical School
      • Department of Pathology & Laboratory Medicine
      Houston, Texas, United States
    • Peking University
      • School of Life Sciences
      Beijing, Beijing Shi, China
  • 2006
    • Wuhan Institute Of Virology
      Wu-han-shih, Hubei, China
  • 2004
    • Zhongshan University
      中山, Guangdong, China
  • 1993–2001
    • Baylor College of Medicine
      • • Program in Structural and Computational Biology and Molecular Biophysics
      • • Department of Biochemistry & Molecular Biology
      Houston, TX, United States
  • 1995–1998
    • University of Houston
      Houston, Texas, United States