Leonard Mindich, Ph.D.

Professor of Microbiology, Biochemistry & Molecular Genetics
mindicle@njms.rutgers.edu

Our group has been interested in two important problems in virology. The first is the nature of the mechanisms of genomic packaging in viruses that have complex RNA genomes. In several cases, viruses can package a multipartite RNA genome such that each virion has one each of the different genomic segments. We studied packaging of the genomes of the Cystoviridae, bacteriophages with a genome composed of three segments of double-stranded RNA. We developed a model for the packaging mechanism and substantiated it experimentally. It is the only case where the mechanism of packaging has been elucidated for a multipartite genome. We used this model to identify the detailed molecular interactions involved in the specificity of the packaging.

The second problem we studied was the temporal regulation of gene expression during viral infection. Proteins that are involved in genome reproduction are usually expressed early in infection, while those involved with lysis or assembly of the cell infection apparatus are expressed later. In the Cystoviridae, the genome is composed of three segments of dsRNA. The largest segment, designated as L codes for four proteins that assemble to form the core of the virus, which is the machine that is responsible for the replication of the viral genome. The transcript of segment L is abundant early in infection and scarce at later times. Our studies revealed that the transcription of L is stimulated by the binding of specific host proteins to the viral core upon infection of the host cell. The host proteins are in short supply and therefore cover only the infecting particles and a few newly formed ones.  Most of the new virions lack the host proteins and therefore primarily transcribe the S and M segments. Four different members of the Cystoviridae each use a different host protein to control the transcription of segment L. Bacteriophage Φ8, which is more distantly related to most members of the Cystoviridae, uses a different mechanism to control the abundance of the L transcript. In this case, the L segment has a unique gene that produces a protein that is involved in the destruction of the L transcript.  We investigated the mechanism by which the host proteins binding to the viral core results in a change in the specific activity of the viral RNA polymerase. We also studied the details of the process by which a Φ8 protein causes the decay of the L transcript.

Qiao J, Mindich L (2013) The template specificity of bacteriophage {phi}6 RNA polymerase. J Virol 87: 10190-10194. PMI: 23864621

Nemecek D, Boura E, Wu W, Cheng N, Plevka P, Qiao J, Mindich L, Heymann JB, Hurley JH, Steven AC (2013) Subunit Folds and Maturation Pathway of a dsRNA Virus Capsid. Structure 21: 1374-1383. PMI: 23891288

Nemecek D, Qiao J, Mindich L, Steven AC, Heymann JB (2012) Packaging accessory protein P7 and polymerase P2 have mutually occluding binding sites inside the bacteriophage 6 procapsid. J Virol 86: 11616-11624. PMI: 22896624

Mindich L (2012) Packaging in dsRNA viruses. Adv Exp Med Biol 726: 601-608. PMI: 22297532

Nemecek D, Cheng N, Qiao J, Mindich L, Steven AC, Heymann JB (2011) Stepwise expansion of the bacteriophage varphi6 procapsid: possible packaging intermediates. J Mol Biol 414: 260-271. PMI: 22019738

Qiao X, Sun Y, Qiao J, Mindich L (2010) Interaction of a host protein with core complexes of bacteriophage phi6 to control transcription. J Virol 84: 4821-4825. PMI: 20164238

Qiao X, Sun Y, Qiao J, Di Sanzo F, Mindich L (2010) Characterization of Phi2954, a newly isolated bacteriophage containing three dsRNA genomic segments. BMC Microbiol 10: 55. PMI: 20170499

Qiao J, Qiao X, Sun Y, Mindich L (2010) Role of host protein glutaredoxin 3 in the control of transcription during bacteriophage Phi2954 infection. Proc Natl Acad Sci U S A 107: 6000-6004. PMI: 20231437

Nemecek D, Heymann JB, Qiao J, Mindich L, Steven AC (2010) Cryo-electron tomography of bacteriophage phi6 procapsids shows random occupancy of the binding sites for RNA polymerase and packaging NTPase. J Struct Biol 171: 389-396. PMI: 20538059

Qiao X, Sun Y, Qiao J, Mindich L (2009) Temporal control of message stability in the life cycle of double-stranded RNA bacteriophage phi8. J Virol 83: 633-639. PMI: 18971268

Sen A, Heymann JB, Cheng N, Qiao J, Mindich L, Steven AC (2008) Initial location of the RNA-dependent RNA polymerase in the bacteriophage Phi6 procapsid determined by cryo-electron microscopy. J Biol Chem 283: 12227-12231. PMI: 18287088

Qiao X, Sun Y, Qiao J, Mindich L (2008) The role of host protein YajQ in the temporal control of transcription in bacteriophage Phi6. Proc Natl Acad Sci U S A 105: 15956-15960. PMI: 18836083

Mindich L (2006) Phages with segmented double-stranded RNA genomes. In Calendar R (ed.), The Bacteriophages. Oxford University Press, New York, pp. 197-207.

Qiao J, Qiao X, Mindich L (2005) In vivo studies of genomic packaging in the dsRNA bacteriophage Phi8. BMC Microbiol 5: 10. PMI: 15762996

Sun Y, Qiao X, Mindich L (2004) Construction of carrier state viruses with partial genomes of the segmented dsRNA bacteriophages. Virology 319: 274-279. PMI: 14980487

Mindich L (2004) Packaging, replication and recombination of the segmented genome of bacteriophage Phi6 and its relatives. Virus Res 101: 83-92. PMI: 15010219

Sun Y, Qiao X, Qiao J, Onodera S, Mindich L (2003) Unique properties of the inner core of bacteriophage phi8, a virus with a segmented dsRNA genome. Virology 308: 354-361. PMI: 12706084

Qiao X, Qiao J, Mindich L (2003) Analysis of specific binding involved in genomic packaging of the double-stranded-RNA bacteriophage phi6. J Bacteriol 185: 6409-6414. PMI: 14563876

Qiao J, Qiao X, Sun Y, Mindich L (2003) Isolation and analysis of mutants of double-stranded-RNA bacteriophage phi6 with altered packaging specificity. J Bacteriol 185: 4572-4577. PMI: 12867467

Onodera S, Sun Y, Mindich L (2001) Reverse genetics and recombination in Phi8, a dsRNA bacteriophage. Virology 286: 113-118. PMI: 11448164

Qiao X, Qiao J, Onodera S, Mindich L (2000) Characterization of phi 13, a bacteriophage related to phi 6 and containing three dsRNA genomic segments. Virology 275: 218-224. PMI: 11017801

Hoogstraten D, Qiao X, Sun Y, Hu A, Onodera S, Mindich L (2000) Characterization of phi8, a bacteriophage containing three double-stranded RNA genomic segments and distantly related to Phi6. Virology 272: 218-224. PMI: 10873764

Mindich L, Qiao X, Qiao J, Onodera S, Romantschuk M, Hoogstraten D (1999) Isolation of additional bacteriophages with genomes of segmented double-stranded RNA. J Bacteriol 181: 4505-4508. PMI: 10419946

Mindich L (1999) Precise packaging of the three genomic segments of the double-stranded-RNA bacteriophage phi6. Microbiol Mol Biol Rev 63: 149-160. PMI: 10066834

Mindich L (1999) Reverse genetics of dsRNA bacteriophage phi 6. Adv Virus Res 53: 341-353. PMI: 10582106

de Haas F, Paatero AO, Mindich L, Bamford DH, Fuller SD (1999) A symmetry mismatch at the site of RNA packaging in the polymerase complex of dsRNA bacteriophage phi6. J Mol Biol 294: 357-372. PMI: 10610764

Paatero AO, Mindich L, Bamford DH (1998) Mutational analysis of the role of nucleoside triphosphatase P4 in the assembly of the RNA polymerase complex of bacteriophage phi6. J Virol 72: 10058-10065. PMI: 9811745

Onodera S, Qiao X, Qiao J, Mindich L (1998) Directed changes in the number of double-stranded RNA genomic segments in bacteriophage phi6. Proc Natl Acad Sci U S A 95: 3920-3924. PMI: 9520468

Onodera S, Qiao X, Qiao J, Mindich L (1998) Isolation of a mutant that changes genomic packaging specificity in phi6. Virology 252: 438-442. PMI: 9878623

Qiao X, Qiao J, Mindich L (1997) An in vitro system for the investigation of heterologous RNA recombination. Virology 227: 103-110. PMI: 9007063

Qiao X, Qiao J, Mindich L (1997) Stoichiometric packaging of the three genomic segments of double-stranded RNA bacteriophage phi6. Proc Natl Acad Sci U S A 94: 4074-4079. PMI: 9108107

Qiao X, Qiao J, Mindich L (1995) Interference with bacteriophage phi 6 genomic RNA packaging by hairpin structures. J Virol 69: 5502-5505. PMI: 7636995

Qiao X, Casini G, Qiao J, Mindich L (1995) In vitro packaging of individual genomic segments of bacteriophage phi 6 RNA: serial dependence relationships. J Virol 69: 2926-2931. PMI: 7707518

Onodera S, Qiao X, Qiao J, Mindich L (1995) Acquisition of a fourth genomic segment in bacteriophage phi 6, a bacteriophage with a genome of three segments of dsRNA. Virology 212: 204-212. PMI: 7676631

Mindich L, Qiao X, Qiao J (1995) Packaging of multiple copies of reduced-size genomic segments by bacteriophage phi 6. Virology 212: 213-217. PMI: 7676632