Please note: The University of Texas Health Science Center at San Antonio will now be called "UT Health San Antonio."

Search Program Faculty/Research

Anthony Griffiths, Ph.D.

Griffiths 2011

RESEARCH

The family Filoviridae includes Ebola virus and Marburg virus, which are associated with sporadic outbreaks and high case fatality rates. A maximum containment laboratory (Biosafety Level-4) is required to study infectious forms of these viruses, and we have a full-suit BSL-4 laboratory at Texas Biomed. Our laboratory is interested in multiple aspects of filovirus biology with a view to exploiting this knowledge to further the development of vaccines and therapeutics.

Typically, RNA viruses have high spontaneous mutation rates due to error prone RNA-dependent RNA polymerases. The consequences of high spontaneous mutation and replication rates are populations composed of heterogeneous swarms of related variant sequences, sometimes called quasispecies. We are investigating the importance of this diversity to filovirus replication and pathogenesis in vitro and in vivo and are particularly interested in exploiting the mutation rate as a therapeutic mechanism. Specifically, we work to understand the roles of the individual genotype populations in virus infection; for example, in any Ebola virus population there is a mixture of genotypes that appear to control the expression of different forms of the virus glycoprotein (GP). The ratios of the genotypes is dynamic and changes dependent on the origin species of cells used to propagate virus, and even in an infected animal. These changes are certainly important for the development of vaccines and therapeutic – that require animal models – but also for viral pathogenesis.

Many of these studies exploit recent advances in sequencing. We have several Illumina sequencing machines on our campus and a miSeq in our laboratory. This system permits quantification of the individual viral genotypes in a sample and we have developed techniques to rapidly sequence whole viral genomes, including the 5’ and 3’ termini. We are expanding the use of these machines into other areas including gene expression and ribosomal profiling of cells and tissues infected with BSL-4 pathogens.

Selected Publications

Alfson KJ, Beadles MW, and A. Griffiths*. (2014) A new approach to determining whole viral genomic sequences including termini using a single deep sequencing run. Journal of Virological Methods. 208 (1), 1-5

Alfson, Beadles, Menzie, Patterson, Carrion, and Griffiths*. (2015)Genetic Changes at the Glycoprotein Editing Site Associated with Serial Passage of Sudan Virus. J Infect Dis. pii: jiv216.

Alfson, Avena, Beadles, Staples, Nunneley, Ticer, Dick, Owston, Reed, Patterson, Carrion, and Griffiths*. (2015) Particle to plaque-forming unit ratio of Ebola virus influences disease course and survival in cynomolgus macaques. Journal of Virology. 89:6773-6781. PMCID: PMCID: PMC4468478 [Available on 2016-01-01]. Selected by journal for Spotlight feature

Cai, Parks, Wall, Stott, Stambaugh, Alfson, Griffiths, Mathies, Carrion, Patterson, Hawking, and Schmidt. (2015)Diagnosis of Ebola virus infection via amplification-free direct detection of single nucleic acids on a chip. Scientific Reports. 5:14494. 1-8.

Colgrove, Liu, Griffiths, Raja, DeLuca, Newman, Coen, and Knipe. (2015) History and genomic sequence analysis of the herpes simplex virus 1 KOS and KOS1.1 sub-strain. Virology. 487. 215-221

Alfson, Worwa, Carrion, and Griffiths*. (2015)Determination of the spontaneous mutation rate of Ebola virus and exploitation of this rate therapeutically. Journal of virology. 90(5):2345-55. Selected by journal for Spotlight feature

Cnops, van Griensven, Honko, Bausch, Sprecher, Hill, Colebunders, Johnson, Griffiths, Palacios, Kraft, Kobinger, Hewlett, Norwood, Sabeti, Jahrling, Formenty, Kuhn, and Arien. (2016) Essentials of filoviral load quantification. Lancet Infectious Diseases. 16(7): e134-e138

Sanabria-Solano, Gonzales, Richerioux, Bertrand, Griffiths, Langelier, and Pearson. (2016) Regulation of viral gene expression by the expression of herpes simplex virus 1 UL24 protein. Virology. 495: 148-160

Harden, Prasad, Griffiths, and Munger. (2017) Modulation of microRNA-mRNA target pairs by human papillomavirus 16 oncoproteins. mBio. 8(1); e02170-16

Du, Cai, Park, Wall, Stott, Alfson, Griffiths, Carrion, Patterson, Hawkins, Schmidt, and Mathies. (2017) Multiplexed efficient on-chop sample preparation and sensitive amplification-free detection of Ebola virus. Biosensors and Bioelectronics. 91; 489-496.

Alfson, Avena, Worwa, Carrion, Griffiths*. Development of a lethal intranasal exposure model of Ebola virus in the cynomolgus macaque. Accepted for publication in Viruses.

Assistant Scientist
Virology and Immunology
Texas Biomedical Research Institute

Education

Ph.D., University of Cambridge

Contact

Email: AGRIFFITHS@TXBIOMED.ORG

Phone: (210) 258-9557

Research Profile
More Info...

Graduate Students

Ashley Silvia

Laura Avena