Michael G. Rossmann's research while affiliated with Purdue University and other places

Publications (638)

Article
Full-text available
Giant viruses are a large group of viruses that infect many eukaryotes. Although components that do not obey the overall icosahedral symmetry of their capsids have been observed and found to play critical roles in the viral life cycles, identities and high-resolution structures of these components remain unknown. Here, by determining a near-atomic-...
Article
Many icosahedral viruses assemble proteinaceous precursors called proheads or procapsids. Proheads are metastable structures that undergo a profound structural transition known as expansion that transforms an immature unexpanded head into a mature genome-packaging head. Bacteriophage T4 is a model virus, well studied genetically and biochemically,...
Article
Alphaviruses can cause severe human arthritis and encephalitis. During virus infection, structural changes of viral glycoproteins in the acidified endosome trigger virus–host membrane fusion for delivery of the capsid core and RNA genome into the cytosol to initiate virus translation and replication. However, mechanisms by which E1 and E2 glycoprot...
Preprint
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Antibiotic resistance poses a growing risk to public health requiring new tools to combat pathogenic bacteria. Contractile injection systems, including bacteriophage tails, pyocins, and bacterial type VI secretion systems, can efficiently penetrate cell envelopes and become potential antibacterial agents. Bacteriophage XM1 is a dsDNA virus belongin...
Conference Paper
Usutu virus (USUV), an arbovirus belonging to the JEV serocomplex of family Flaviviridae, is currently rampant in Europe and increasingly recognized for its pervasive asymptomatic presence in the human population. In rare cases, USUV infection in humans leads to severe disease that involves encephalitis and meningoencephalitis. However, no preventa...
Article
Significance Usutu virus (USUV) was first identified in Africa in 1959; however, multiple, independent introductions via migratory birds and vector proliferation facilitated by climate change expanded the ecological niche of USUV across Europe. In humans, some African USUV lineages typically cause mild disease; however, the European strains, marked...
Article
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Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from...
Article
Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease burden, no approved therapies or licensed vaccines exist. Here, we describe human monoclonal antibodies (mAbs) that bind to and neutralize multiple distant...
Article
Enterovirus D68 (EV-D68) causes outbreaks of respiratory illness, and there is increasing evidence that it causes outbreaks of acute flaccid myelitis (AFM). There are no licensed therapies to prevent or treat EV-D68 infection or AFM disease. We isolated a panel of EV-D68–reactive human monoclonal antibodies that recognize diverse antigenic variants...
Article
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Large biological structures are assembled from smaller, often symmetric, sub-structures. However, asymmetry among sub-structures is fundamentally important for biological function. An extreme form of asymmetry, a 12-fold-symmetric dodecameric portal complex inserted into a 5-fold-symmetric capsid vertex, is found in numerous icosahedral viruses, in...
Article
Eastern equine encephalitis virus (EEEV), a mosquito-borne icosahedral alphavirus found mainly in North America, causes human and equine neurotropic infections. EEEV neurovirulence is influenced by the interaction of the viral envelope protein E2 with heparan sulfate (HS) proteoglycans from the host’s plasma membrane during virus entry. Here, we pr...
Article
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Infection by Rhinovirus-C (RV-C), a species of Picornaviridae Enterovirus , is strongly associated with childhood asthma exacerbations. Cellular binding and entry by all RV-C, which trigger these episodes, is mediated by the first extracellular domain (EC1) of cadherin-related protein 3 (CDHR3), a surface cadherin-like protein expressed primarily o...
Chapter
Viruses have complex molecular architectures and have evolved to be ubiquitous parasites of all life forms. They consist of a genome enclosed in a protein or a proteolipid shell. In the 1950s, Watson and Crick as well as Caspar and Klug postulated the basic principles of virus structure organization. The last six decades have seen an exponential in...
Article
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Tailed bacteriophages (phages) are one of the most abundant life forms on Earth. They encode highly efficient molecular machines to infect bacteria, but the initial interactions between a phage and a bacterium that then lead to irreversible virus attachment and infection are poorly understood. This information is critically needed to engineer machi...
Preprint
Tailed bacteriophages (phages) are one of the most abundant life forms on Earth. They encode highly efficient molecular machines to infect bacteria, but the initial interactions between a phage and a bacterium that then lead to irreversible virus attachment and infection are poorly understood. This information is critically needed to engineer machi...
Preprint
Tailed bacteriophages (phages) are one of the most abundant life forms on Earth. They encode highly efficient molecular machines to infect bacteria, but the initial interactions between a phage and a bacterium that then lead to irreversible virus attachment and infection are poorly understood. This information is critically needed to engineer machi...
Preprint
Tailed bacteriophages (phages) are one of the most abundant life forms on Earth. They encode highly efficient molecular machines to infect bacteria, but the initial interactions between a phage and a bacterium that then lead to irreversible virus attachment and infection are poorly understood. This information is critically needed to engineer machi...
Article
Full-text available
Enteroviruses are a major cause of human disease. Adipose-specific phospholipase A2 (PLA2G16) was recently identified as a pan-enterovirus host factor and potential drug target. In this study, we identify a possible mechanism of PLA2G16 evasion by employing a dual glycan receptor-binding enterovirus D68 (EV-D68) strain. We previously showed that th...
Article
Epstein-Barr virus (EBV)causes infectious mononucleosis and is associated with epithelial-cell cancers and B cell lymphomas. An effective EBV vaccine is not available. We found that antibodies to the EBV glycoprotein gH/gL complex were the principal components in human plasma that neutralized infection of epithelial cells and that antibodies to gH/...
Article
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Parvovirus B19, one of the most common human pathogens, is a small DNA virus that belongs to the Parvoviridae . As a result of previous infections, antibodies to B19 are present in most adults. B19 has a strong tropism to erythroid progenitor cells and is able to cause a series of medical conditions including fifth disease, arthritis, myocarditis,...
Article
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The envelope protein of human immunodeficiency virus-1 (HIV-1) and its fusion peptide are essential for cell entry and vaccine design. Here, we describe the 3.9-Å resolution structure of an envelope protein trimer from a very early transmitted founder virus (CRF01_AE T/F100) complexed with Fab from the broadly neutralizing antibody (bNAb) 8ANC195....
Article
The interpretation of cryo-electron tomograms of macromolecular complexes can be difficult because of the large amount of noise and because of the missing wedge effect. Here it is shown how the presence of rotational symmetry in a sample can be utilized to enhance the quality of a tomographic analysis. The orientation of symmetry axes in a sub-tomo...
Article
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Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structu...
Article
Zika virus (ZIKV) is a major human pathogen and member of the Flavivirus genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Ba...
Article
Enterovirus D68 (EV-D68) belongs to a group of enteroviruses that contain a single positive-sense RNA genome surrounded by an icosahedral capsid. Like common cold viruses, EV-D68 mainly causes respiratory infections and is acid-labile. The molecular mechanism by which the acid-sensitive EV-D68 virions uncoat and deliver their genome into a host cel...
Article
Full-text available
p>Alphaviruses are enveloped pathogens that cause arthritis and encephalitis. Here, we report a 4.4-Å cryoelectron microscopy (cryo-EM) structure of eastern equine encephalitis virus (EEEV), an alphavirus that causes fatal encephalitis in humans. Our analysis provides insights into viral entry into host cells. The envelope protein E2 showed a bindi...
Article
Flaviviruses assemble initially in an immature, noninfectious state and undergo extensive conformational rearrangements to generate mature virus. Previous cryo-electron microscopy (cryo-EM) structural studies of flaviviruses assumed icosahedral symmetry and showed the concentric organization of the external glycoprotein shell, the lipid membrane, a...
Preprint
Enterovirus D68 (EV-D68) belongs to a group of enteroviruses that contain a single positive-sense RNA genome surrounded by an icosahedral capsid. Like common cold viruses, EV-D68 mainly causes respiratory infections and is acid labile. The molecular mechanism by which the acid sensitive EV-D68 virions uncoat and deliver their genome into a host cel...
Article
Among the several arthropod-borne human flaviviral diseases, the recent outbreak of Zika virus (ZIKV) has caused devastating birth defects and neurological disorders, challenging the world with another major public health concern. We report here the refined structure of the mature ZIKV at a resolution of 3.1 Å as determined by cryo-electron microsc...
Article
Full-text available
The Ewald sphere effect is generally neglected when using the Central Projection Theorem for cryo electron microscopy single-particle reconstructions. This can reduce the resolution of a reconstruction. Here we estimate the attainable resolution and report a "block-based" reconstruction method for extending the resolution limit. We find the Ewald s...
Article
Zika virus (ZIKV) is an enveloped, icosahedral flavivirus that has structural and functional similarities to other human flavivirus pathogens such as dengue (DENV), West Nile (WNV) and Japanese encephalitis (JEV) viruses. ZIKV infections have been linked to fetal microcephaly and the paralytic Guillain-Barré syndrome. This review provides a compara...
Article
Significance The three-dimensional structure of Vp54, the major capsid protein of the chlorovirus Paramecium bursaria chlorella virus (PBCV-1), was determined by combining two powerful techniques, X-ray diffraction and carbohydrate molecular modeling. This strategy resolved the limitations posed by each technique alone and increases our understandi...
Article
Significance One of the unresolved mysteries of tailless bacteriophages is how they recognize potential targets and translocate their genomes across the periplasmic space of their hosts. In this study, bilayers consisting of lipopolysaccharides (LPS) derived from bacterial cells were found to trigger genome ejection from ΦX174. We investigated the...
Article
Full-text available
Significance Chikungunya virus (CHIKV) belongs to the alphavirus family, the members of which have enveloped icosahedral capsids. The maturation process of alphaviruses involves proteolysis of some of the structural proteins before assembling with nucleocapsids to produce mature virions. We mutated the proteolytic cleavage site on E2 envelope prote...
Article
Marine bacteriophage TW1 belongs to the Siphoviridae family and infects Pseudoalteromonas phenolica. Mass spectrometry analysis has identified 16 different proteins in the TW1 virion. Functions of most of these proteins have been predicted by bioinformatic methods. A 3.6 Å resolution cryoelectron microscopy map of the icosahedrally averaged TW1 hea...
Article
Full-text available
Significance The WT bacteriophage T4 head is prolate with icosahedral T=13 ends closing the central cylindrical section. The structure of a T=13 icosahedral head assembly, in which the major capsid protein of T4 phage had a single mutation at a residue in the interface between neighboring subunits, has been determined to 3.3-Å resolution. The struc...
Article
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Significance Rhinoviruses (RVs) frequently cause respiratory infections in humans. However, there are currently no approved antiviral treatments or vaccines available. Using cryo-electron microscopy (cryo-EM), we have shown that the antigen-binding fragment of a neutralizing antibody, C5, binds to RV-B14 and causes significant structural rearrangem...
Data
Fitting of the capsid protein’s C-terminal domain into the sub-tomogram averaged capsid density. Left and right panel show the two best fit orientations of the capsid protein structure into one lobe of the capsid unit density. (TIF)
Article
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Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a hel...
Data
Model representing the relationship between glycoproteins on the virion surface and the internal nucleocapsid units. (A and B) The virions represented here are the same as in Fig 4B and 4C, respectively. Left panel shows a tomogram section at the surface of the rubella virions; the right panel shows a section at the nucleocapsid surface. Scale bars...
Data
Surface representation of the averaged density of rubella virus glycoprotein rows (in blue). The atomic model of the rubella E1 glycoprotein (red) is placed into one of the subunits of the averaged density to show that the averaged volume of the rubella glycoprotein rows only covers about half the volume of the E1 structure. The left and right pane...
Data
Fit of atomic structures to sub-tomogram averaged density. (DOCX)
Data
Resolution of the sub-tomogram averaged glycoprotein spike. Fourier Shell Correlation (FSC) curve (gold-standard) between the masked averages from two independent half-sets of the glycoprotein spikes. The dashed line at 0.143 FSC intersects the curve at 11.0 Å. (TIF)
Data
Glycoprotein spike intermediate volumes from the sub-tomogram averaging procedure. From top left to bottom right: The top left panel shows the initial model derived from 256 initial spikes. The next three panels show the updated reference models derived from 2/3rd of the total sub-volumes for iterations 3, 5 and 7. The bottom middle panel shows the...
Data
Surface representation of an unaveraged long rubella virion. (MP4)
Data
Agarose gel analysis of in vitro assembled nucleocapsid cores. Left panel is an agarose gel under UV illumination to show the presence of nucleic acids. The right panel shows the same gel after Coomassie blue staining to indicate presence of protein. Lane 1: 1kb DNA ladder, Lanes 2 and 4: purified nucleocapsid cores, Lanes 3 and 5: purified nucleoc...
Data
Surface representation of an unaveraged, partially tubular rubella virion. (MP4)
Data
Surface representation of an unaveraged, small, pseudo-spherical rubella virion. (MP4)
Article
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Virus-like particles (VLPs) are non-infectious multiprotein structures that are engineered to self-assemble from viral structural proteins. Here, we developed a novel VLP-based vaccine platform utilizing VLPs from the Chikungunya virus. We identified two regions within the envelope protein, a structural component of Chikungunya, where foreign antig...
Article
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African swine fever virus , a double stranded DNA virus infecting pigs, is the only known member of the Asfarviridae family. Nevertheless, during our isolation and sequencing of the complete genome of Faustovirus followed by the description of Kaumoebavirus, carried out over the past two years, we observed the emergence of previously unknown relate...
Article
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The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimens...
Article
The current Zika virus (ZIKV) epidemic is characterized by severe pathogenicity in both children and adults. Sequence changes in ZIKV since its first isolation are apparent when pre-epidemic strains are compared with those causing the current epidemic. However, the residues that are responsible for ZIKV pathogenicity are largely unknown. Here we re...
Article
Many large viruses, including tailed dsDNA bacteriophages and herpesviruses, assemble their capsids via formation of precursors, called procapsids or proheads. The prohead has an internal core, made of scaffolding proteins, and an outer shell, formed by the major capsid protein. The prohead usually contains a protease, which is activated during cap...
Article
The tail of bacteriophage T4 undergoes large structural changes upon infection while delivering the phage genome into the host cell. The baseplate is located at the distal end of the contractile tail and plays a central role in transmitting the signal to the tail sheath that the tailfibers have been adsorbed by a host bacterium. This then triggers...
Article
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Significance The recently identified rhinovirus C (RV-C) species of picornaviruses might be associated with more severe respiratory infections than other rhinoviruses in children. The RV-C have been linked to 50–85% of hospital-level childhood asthma exacerbations that can lead to significant adult respiratory problems. However, there are currently...
Article
Full-text available
Significance Since the discovery of Mimivirus in 2003, many new giant viruses have been isolated and characterized, now that the definition of viruses excludes their ability to pass through the finest available filters. At least one of these viruses can cause serious infections. Here we describe the structure of faustovirus, the prototypic member o...
Article
Unveiling the Zika virus The ongoing Zika virus epidemic is of grave concern because of its apparent links to congenital microcephaly and Guillain-Barré syndrome. Sirohi et al. present a near-atomic-resolution structure of mature Zika virus determined by cryo-electron microscopy. The structure is mainly similar to that of other flaviviruses such as...
Article
Significance This study examines how the high-energy, dome-shaped infectious form of the bacteriophage T4 baseplate assembles as opposed to how it assembles in the low-energy, star-shaped form that occurs after infection. Normal expectations would be that a molecular assembly occurs as a result of loss of energy. However, a virus has to be poised i...
Article
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Significance Enterovirus D68 (EV-D68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the United States and is associated with cases of paralysis. Little is known about EV-D68 host factor requirements. Here, using a genome-wide knockout approach, we identified several genes in sialic acid (Sia) biology...