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Morphology and ultrastructure of retrovirus particles.

Zhang W, Cao S, Martin JL, Mueller JD, Mansky LM - AIMS Biophys (2015)

Bottom Line: Retrovirus morphogenesis entails assembly of Gag proteins and the viral genome on the host plasma membrane, acquisition of the viral membrane and envelope proteins through budding, and formation of the core through the maturation process.The heterogeneity of retroviruses poses significant challenges to studying the protein contacts within the Gag and capsid lattices.Also reviewed are morphological studies of retrovirus budding, maturation, infection and cell-cell transmission, which inform the structural transformation of the viruses and the cells during infection and viral transmission, and lead to better understanding of the interplay between the functioning viral proteins and the host cell.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Molecular Virology, University of Minnesota, Minneapolis, MN, USA ; Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA ; Characterization Facility, University of Minnesota, Minneapolis, MN, USA.

ABSTRACT

Retrovirus morphogenesis entails assembly of Gag proteins and the viral genome on the host plasma membrane, acquisition of the viral membrane and envelope proteins through budding, and formation of the core through the maturation process. Although in both immature and mature retroviruses, Gag and capsid proteins are organized as paracrystalline structures, the curvatures of these protein arrays are evidently not uniform within one or among all virus particles. The heterogeneity of retroviruses poses significant challenges to studying the protein contacts within the Gag and capsid lattices. This review focuses on current understanding of the molecular organization of retroviruses derived from the sub-nanometer structures of immature virus particles, helical capsid protein assemblies and soluble envelope protein complexes. These studies provide insight into the molecular elements that maintain the stability, flexibility and infectivity of virus particles. Also reviewed are morphological studies of retrovirus budding, maturation, infection and cell-cell transmission, which inform the structural transformation of the viruses and the cells during infection and viral transmission, and lead to better understanding of the interplay between the functioning viral proteins and the host cell.

No MeSH data available.


Related in: MedlinePlus

Structure of Gag lattice within immature HIV-1. (A) Computational slice through a Gaussian-filtered tomogram containing immature HIV-1 particles treated with the protease inhibitor amprenavir [67]. The white arrow marks a slice through the CA layer illustrating the hexagonal lattice. Defects of the Gag lattice are evident in these particles. Figure courtesy of John Briggs. (B–D) Surface rendering of the reconstruction of immature HIV-1 particle [31]. Adapted by permission from the journal. (B) A cross section perpendicular to the membrane. RNP represents ribonucleoprotein complex. (C) Surface cut tangential to the membrane at a radius indicated by the black dash line in B, and looking down on the NTDs of the CA lattice. (D) Surface cut through the CTDs of the CA lattice. (E) Surface rendering of the CA organization in the HIV-1 (EMD-2706) and MPMV (EMD-2707) immature particles [67], viewed from the same position shown in C. The CTDs in both viruses are colored in orange, while the NTDs of CA in HIV-1 and MPMV is colored in blue and green respectively. The numbers represent two-fold, three-fold and six-fold symmetry axes. These figures are produced using UCSF Chimera [68].
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Figure 3: Structure of Gag lattice within immature HIV-1. (A) Computational slice through a Gaussian-filtered tomogram containing immature HIV-1 particles treated with the protease inhibitor amprenavir [67]. The white arrow marks a slice through the CA layer illustrating the hexagonal lattice. Defects of the Gag lattice are evident in these particles. Figure courtesy of John Briggs. (B–D) Surface rendering of the reconstruction of immature HIV-1 particle [31]. Adapted by permission from the journal. (B) A cross section perpendicular to the membrane. RNP represents ribonucleoprotein complex. (C) Surface cut tangential to the membrane at a radius indicated by the black dash line in B, and looking down on the NTDs of the CA lattice. (D) Surface cut through the CTDs of the CA lattice. (E) Surface rendering of the CA organization in the HIV-1 (EMD-2706) and MPMV (EMD-2707) immature particles [67], viewed from the same position shown in C. The CTDs in both viruses are colored in orange, while the NTDs of CA in HIV-1 and MPMV is colored in blue and green respectively. The numbers represent two-fold, three-fold and six-fold symmetry axes. These figures are produced using UCSF Chimera [68].

Mentions: The most detailed models of immature Gag lattices are based on the structures of in vitro-assembled tubular arrays of MPMV CA-NC proteins at 8 Å resolution [12] and the immature HIV-1 capsid within intact virus particles at 8.8 Å resolution (Figure 3 A and E) [67]. The structures of MPMV CA-NC tubes were determined using two methods: helical reconstruction [12] and tomography followed by sub-tomogram averaging [76]. The validity of the modeled MPMV Gag lattice within the tubular structure was confirmed by reconstruction of protease-inhibited immature MPMV virions [67]. Although amino acid conservation between CA proteins from different viral genera is poor, the secondary and tertiary structures are highly conserved [21]. A retrovirus NTD contains seven α-helices and a β-hairpin, while the CTD contains four α-helices and a flexible linker connecting the NTD (Figure 4 A) [72]. The high resolution of these cryo-EM reconstruction maps enabled unambiguous fitting of the atomic structures of the HIV-1 NTD [77] and CTD [78], the NMR structure of the MPMV NTD [79] and the homology model of the MPMV CTD, based on the HIV-1 CTD structure [12,78]. The fitting revealed the positions of the two CA domains and led to generation of pseudo-atomic models of the immature CA lattice in both viruses. These available Gag lattices suggest similar hexameric arrangement of the CTDs in MPMV and HIV-1, but different NTD configurations.


Morphology and ultrastructure of retrovirus particles.

Zhang W, Cao S, Martin JL, Mueller JD, Mansky LM - AIMS Biophys (2015)

Structure of Gag lattice within immature HIV-1. (A) Computational slice through a Gaussian-filtered tomogram containing immature HIV-1 particles treated with the protease inhibitor amprenavir [67]. The white arrow marks a slice through the CA layer illustrating the hexagonal lattice. Defects of the Gag lattice are evident in these particles. Figure courtesy of John Briggs. (B–D) Surface rendering of the reconstruction of immature HIV-1 particle [31]. Adapted by permission from the journal. (B) A cross section perpendicular to the membrane. RNP represents ribonucleoprotein complex. (C) Surface cut tangential to the membrane at a radius indicated by the black dash line in B, and looking down on the NTDs of the CA lattice. (D) Surface cut through the CTDs of the CA lattice. (E) Surface rendering of the CA organization in the HIV-1 (EMD-2706) and MPMV (EMD-2707) immature particles [67], viewed from the same position shown in C. The CTDs in both viruses are colored in orange, while the NTDs of CA in HIV-1 and MPMV is colored in blue and green respectively. The numbers represent two-fold, three-fold and six-fold symmetry axes. These figures are produced using UCSF Chimera [68].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4593330&req=5

Figure 3: Structure of Gag lattice within immature HIV-1. (A) Computational slice through a Gaussian-filtered tomogram containing immature HIV-1 particles treated with the protease inhibitor amprenavir [67]. The white arrow marks a slice through the CA layer illustrating the hexagonal lattice. Defects of the Gag lattice are evident in these particles. Figure courtesy of John Briggs. (B–D) Surface rendering of the reconstruction of immature HIV-1 particle [31]. Adapted by permission from the journal. (B) A cross section perpendicular to the membrane. RNP represents ribonucleoprotein complex. (C) Surface cut tangential to the membrane at a radius indicated by the black dash line in B, and looking down on the NTDs of the CA lattice. (D) Surface cut through the CTDs of the CA lattice. (E) Surface rendering of the CA organization in the HIV-1 (EMD-2706) and MPMV (EMD-2707) immature particles [67], viewed from the same position shown in C. The CTDs in both viruses are colored in orange, while the NTDs of CA in HIV-1 and MPMV is colored in blue and green respectively. The numbers represent two-fold, three-fold and six-fold symmetry axes. These figures are produced using UCSF Chimera [68].
Mentions: The most detailed models of immature Gag lattices are based on the structures of in vitro-assembled tubular arrays of MPMV CA-NC proteins at 8 Å resolution [12] and the immature HIV-1 capsid within intact virus particles at 8.8 Å resolution (Figure 3 A and E) [67]. The structures of MPMV CA-NC tubes were determined using two methods: helical reconstruction [12] and tomography followed by sub-tomogram averaging [76]. The validity of the modeled MPMV Gag lattice within the tubular structure was confirmed by reconstruction of protease-inhibited immature MPMV virions [67]. Although amino acid conservation between CA proteins from different viral genera is poor, the secondary and tertiary structures are highly conserved [21]. A retrovirus NTD contains seven α-helices and a β-hairpin, while the CTD contains four α-helices and a flexible linker connecting the NTD (Figure 4 A) [72]. The high resolution of these cryo-EM reconstruction maps enabled unambiguous fitting of the atomic structures of the HIV-1 NTD [77] and CTD [78], the NMR structure of the MPMV NTD [79] and the homology model of the MPMV CTD, based on the HIV-1 CTD structure [12,78]. The fitting revealed the positions of the two CA domains and led to generation of pseudo-atomic models of the immature CA lattice in both viruses. These available Gag lattices suggest similar hexameric arrangement of the CTDs in MPMV and HIV-1, but different NTD configurations.

Bottom Line: Retrovirus morphogenesis entails assembly of Gag proteins and the viral genome on the host plasma membrane, acquisition of the viral membrane and envelope proteins through budding, and formation of the core through the maturation process.The heterogeneity of retroviruses poses significant challenges to studying the protein contacts within the Gag and capsid lattices.Also reviewed are morphological studies of retrovirus budding, maturation, infection and cell-cell transmission, which inform the structural transformation of the viruses and the cells during infection and viral transmission, and lead to better understanding of the interplay between the functioning viral proteins and the host cell.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Molecular Virology, University of Minnesota, Minneapolis, MN, USA ; Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA ; Characterization Facility, University of Minnesota, Minneapolis, MN, USA.

ABSTRACT

Retrovirus morphogenesis entails assembly of Gag proteins and the viral genome on the host plasma membrane, acquisition of the viral membrane and envelope proteins through budding, and formation of the core through the maturation process. Although in both immature and mature retroviruses, Gag and capsid proteins are organized as paracrystalline structures, the curvatures of these protein arrays are evidently not uniform within one or among all virus particles. The heterogeneity of retroviruses poses significant challenges to studying the protein contacts within the Gag and capsid lattices. This review focuses on current understanding of the molecular organization of retroviruses derived from the sub-nanometer structures of immature virus particles, helical capsid protein assemblies and soluble envelope protein complexes. These studies provide insight into the molecular elements that maintain the stability, flexibility and infectivity of virus particles. Also reviewed are morphological studies of retrovirus budding, maturation, infection and cell-cell transmission, which inform the structural transformation of the viruses and the cells during infection and viral transmission, and lead to better understanding of the interplay between the functioning viral proteins and the host cell.

No MeSH data available.


Related in: MedlinePlus