Bernard Moss, M.D., Ph.D.

Bernard Moss, M.D., Ph.D.

Chief, Genetic Engineering Section

Major Areas of Research

  • Replication of poxviruses
  • Viral immune defense proteins
  • Recombinant vaccines

Program Description

The goals are to determine the mechanisms used by viruses to infect cells, express and replicate their genomes, assemble infectious particles, and evade the host immune response. Basic information obtained from these studies is used to design antiviral agents and live and subunit recombinant vaccines. In addition, viruses are engineered as expression vectors for biotechnology.

Poxviruses have provided unique opportunities to combine molecular, genetic, microscopic, and immunologic approaches to achieve many of the above goals. Recent studies have also been directed to the characterization and testing of candidate vaccines for human and simian immunodeficiency viruses.

Replicaton Cycle of Orthopoxviruses

Replicaton Cycle of Orthopoxviruses

Credit
NIAID

Virions—containing a double-stranded DNA genome, enzymes, and transcription factors—attach to cells and fuse with the cell membrane, releasing cores into the cytoplasm. The cores synthesize early mRNAs that are translated into a variety of proteins, including growth factors, immune defense molecules, enzymes, and factors for DNA replication and intermediate transcription. Uncoating occurs, and the DNA is replicated to form concatemeric molecules. Intermediate genes in the progeny DNA are transcribed, and the mRNAs are translated to form late transcription factors. The late genes are transcribed and the mRNAs are translated to form virion structural proteins, enzymes, and early transcription factors. Assembly begins with the formation of discrete membrane structures. The concatemeric DNA intermediates are resolved into unit genomes and packaged in immature virions. Maturation proceeds to the formation of infectious intracellular mature virions (MVs). The virions are wrapped by modified trans-Golgi and endosomal cisternae, and the wrapped virions (WVs) are transported to the periphery of the cell via microtubules. Fusion of the wrapped virions with the plasma membrane results in release of extracellular enveloped virions (EVs).

Biography

Dr. Moss received his M.D. from the New York University School of Medicine, interned at the Children's Hospital Medical Center (Boston), and then earned a Ph.D. in biochemistry from the Massachusetts Institute of Technology. He became interested in viruses after joining NIH and is well known for studies on the cap structure of mRNAs, regulation of gene expression, replication cycle of poxviruses, virus defense molecules, and development and application of virus vectors.

Dr. Moss has received numerous awards and prizes, including the Dickson Prize for Medical Research, the Invitrogen Eukaryotic Expression Award, the ICN International Prize in Virology, the Taylor International Prize in Medicine, the Bristol-Myers Squibb Award for Distinguished Achievement in Infectious Disease Research, and the International Poxvirus, Asfarvirus and Iridovirus Lifetime Achievement Award. He was elected to the National Academy of Sciences, American Academy of Microbiology, Fellow of the American Association for the Advancement of Science, and president of the American Society for Virology.

Dr. Moss is currently an editor of Virology and a member of the editorial boards of the Journal of VirologyAIDS Research and Human RetrovirusesCurrent Opinion in BiotechnologyAdvances in Virus Research, and the NIH Catalyst. He is an adjunct professor at George Washington University and the University of Maryland.

Special Interest Groups: Cell Biology, Virology, Vaccine Research

Research Group

Members of Genetic Engineering Section Research Group

Members of Genetic Engineering Section Research Group

Credit
NIAID

From left to right:

Row 1: Sharon Melamed, Visiting Scientist; Pat Earl, Staff Scientist; Bernie Moss, Section Head; Jerry Sisler, Microbiologist; Jeffrey Americo, Biologist; Catherine Cotter, Biologist.
Row 2: Linda Wyatt, Staff Scientist; Wei Xiao, Biologist; Sara Reynolds, Graduate Student.
Row 3: George Katsafanas, Biologist; Liliana Maruri-Avidal, Postdoctoral Fellow; Jorge Mendez-Rios, Graduate student; Shin-Wu Liu, postdoctoral fellow.
Row 4: Cindy Wolfe, Postdoctoral Fellow; Andrea Weisberg, Electron Microscopist; Gilad Sivan, Postdoctoral Fellow; Robin Kastenmeyer, Veterinarian; Zhilong Yang, Postdoctoral Fellow.
Row 5: Karl Erlandson, Postdoctoral Fellow; Tatiana (Senkevich) Koonin; Staff Scientist; Amanda Howard; Postdoctoral Fellow; P.S. Satheshkumar, Postdoctoral Fellow; Jason Laliberte, Postdoctoral Fellow.

Selected Publications

Liu SW, Katsafanas GC, Liu R, Wyatt LS, Moss B. 2015. “Poxvirus decapping enzymes enhance virulence by preventing the accumulation of dsRNA and the induction of innate antiviral responses.Cell Host Microbe 17:320-331.

Senkevich TG, Bruno D, Martens C, Porcella SF, Wolf YI, Moss B. 2015. “Mapping vaccinia virus DNA replication origins at nucleotide level by deep sequencing.Proc Natl Acad Sci USA 112:10908-10913.

Sivan G, Ormanoglu P, Buehler EC, Martin SE, Moss B. 2015. “Identification of restriction factors by human genome-wide RNA interference screening of viral host range mutants exemplified by discovery of SAMD9 and WDR6 as inhibitors of the vaccinia virus K1L-C7L- mutant.MBio 6:e01122.

Yang Z, Cao S, Martens CA, Porcella SF, Xie Z, Ma M, Shen B, Moss B. 2015. “Deciphering poxvirus gene expression by RNA sequencing and ribosome profiling.J Virol 89:6874-6886.

Erlandson KJ, Bisht H, Weisberg AS, Hyun SI, Hansen BT, Fischer ER, Hinshaw JE, Moss B. 2016. “Poxviruses encode a reticulon-like protein that promotes membrane curvature.Cell Rep 14:2084-2091.

Liu R, Moss B. 2016. “Opposing roles of double-stranded RNA effector pathways and viral defense proteins revealed with CRISPR/Cas9 knock-out cell lines and vaccinia virus mutants.” J Virol 90:7864-7879.

Sivan G, Weisberg AS, Americo JL, Moss B. 2016. “Retrograde transport from early endosomes to the trans-Golgi network enables membrane wrapping and egress of vaccinia virions.J Virol 90:8891-8905.

Visit PubMed for a complete publication listing.

Videos

Visualization of movement of fluorescently-labeled wrapped virions (IEV) from factory region to periphery of the cell

At 12 hours after infection, images were collected at 1 frame/sec for a period of 110 sec.

From Ward BM, Moss B. Visualization of intracellular movement of vaccinia virus virions containing a green fluorescent protein-B5R membrane protein chimera. J Virol. 2001 May; 75(10):4802-13.

 

Visualization of fluorescently labeled actin tails tipped by vaccinia virions

At 12 h after infection, images were collected at 1 frame/sec.

From Ward BM, Moss B. Vaccinia virus intracellular movement is associated with microtubules and independent of actin tails. J Virol. 2001 Dec;75(23):11651-63.

 

Rotating 3D model of an A-Type inclusion (ATI) body with embedded with vaccinia virions in a HeLa cell

The IMARIS Surfaces feature was used to define the ATI as a region of interest, which is depicted visually in the model as a red shell. The virions fluorescing green are within and outside the ATI shell.

From Howard A, Moss B. Formation of orthopoxvirus cytoplasmic A-type inclusion bodies and embedding of virions are dynamic processes requiring microtubules. J Virol. 2012 May;86(10):5905-14.

 

Time lapse video of ATI coalescence

Infected cells were imaged as Z-stacks at 20 minute intervals for 4 hours. IMARIS Surfaces was used to track an individual ATI (dragontail) and measure virion embedment as fluorescence within the defined surface over time. ATIs, red; Virions, green.

From Howard A, Moss B. Formation of orthopoxvirus cytoplasmic A-type inclusion bodies and embedding of virions are dynamic processes requiring microtubules. J Virol. 2012 May;86(10):5905-14.

 

Saltatory movement of virions to ATIs

Video shows a virion tracked using the IMARIS Spots feature move to and associate with an ATI.

From Howard A, Moss B. Formation of orthopoxvirus cytoplasmic A-type inclusion bodies and embedding of virions are dynamic processes requiring microtubules. J Virol. 2012 May;86(10):5905-14.

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