Research Professor of Microbiology and Pathobiology
Director, Interdisciplinary Research Training, Fred Hutchinson Cancer Research Center
Member, Division of Basic Sciences, Fred Hutchinson Cancer Research Center
Office Location: B3-105, Fred Hutchinson Cancer Research Center
Campus Box: 358080
Dr. Linial received her B.S. in bacteriology from Cornell and her Ph.D. in microbiology and molecular biology from Tufts. She did postdoctoral research with Dr. P. K. Vogt. At present she combines her association with the Department of Microbiology with a primary appointment as Member in the Division of Basic Sciences at the Fred Hutchinson Cancer Research Center, and an appointment in the Department of Pathobiology.
Our laboratory is interested in the replication and biology of foamy viruses. These complex retroviruses comprise their own subfamily. Foamy viruses (FV) are prevalent in most primate species, and in some accidentally infected humans, as well as in cats, horses, and cows. These viruses are cytopathic to fibroblasts in culture, but do not have deleterious effects on the growth of some other cell types. Many FV have been molecularly cloned, and have been developed as vectors. In particular, their broad host range and lack of pathogenicity are attractive features for human gene therapy. Our lab works on the molecular biology of viral replication, as well as the biology of viral replication in macaques, and the epidemiology of zoonosis.
Foamy viruses appear to occupy a unique niche quite distinct from all other groups of retroviruses. Although their genomes are similar to other complex retroviruses, such as HIV, they have many unique features. Aspects of their replication are more similar to that of the hepadnaviruses such as HBV than to other retroviruses. For example, the mechanism of expression of their reverse transcriptase from a specific, spliced mRNA has not been seen in any other reverse transcriptase encoding virus. In addition, unlike either HIV or HBV, FV requires the Env proteins, but not the Pol proteins, to bud from cells. We have also found that the functional genome of FV is DNA rather than RNA, clearly setting it apart from other retroviruses. We are focusing on understanding the steps in FV assembly and also the unique properties of the viral reverse transcriptase, which is a highly processive enzyme whose synthesis is regulated in an interesting manner. FV assembly intracellularly near the centrioles, and assembled particles are then transported to intracellular vesicles for acquisition of envelope glycoproteins. The details of this pathway are under investigation.
We are interested in determining how FV can establish life long persistent infections without ensuing pathology. Study in our lab of naturally FV infected rhesus macaques has revealed that there are high levels of virus in the oral tissues and in saliva (which is the route of transmission), but not in any other tissues. Interestingly, in SIV immunosuppressed macaques, FV is also found in the jejunum. The details of viral replication, and its consequences are under investigation.
In collaboration with investigators at the University of Washington Primate Center, we have initiated investigations of FV transmission from macaques to humans in areas of Asia where such contacts are abundant. We have found that about 3% of humans with high levels of contacts with monkeys are infected with FV. Future studies will address the issues of human to human viral transmission.
Murray, S.M., Picker, L.J., Axthelm, M.K., and Linial, M.L. Expanded tissue targets for foamy virus replication with SIV induced immunosuppression, J. Virol. 80:663-670, 2006.
Yu, S.F., Eastman, S.W., and Linial, M.L. Foamy virus capsid assembly occurs at a pericentriolar region through a cytoplasmic/targeting retention signal in Gag. Traffic 7:966-977, 2006.
Murray, S.M., Picker, L.J., Axthelm, M.K., Loya-Hudkins, K., Alpers, C. and Linial, M.L. Replication in a superficial epithelial cell niche explains the lack of pathogenicity of primate foamy virus infections, J. Virol. 82:5981-5985, 2008.
E.-G. Lee, D. Kuppers, M. Horn, J. Roy, C. May and M.L. Linial. A premature termination codon at the C-terminus of foamy virus Gag down-regulates the levels of spliced pol mRNA. J. Virol. 82:1656-1664, 2008.
Jones-Engel, L., Steinkraus, K.A., Engel, G.A.,May, C. Rompis, A., Putra, A., Wandia, N., Schillaci, M.A., Fuentes, A., Allan, J., Wilson, B., White, R., Chalise, M., Kyes, R., Aggimarangsee N., Sutthipat, T., Somgird, C., Grant, R., Watanabe, R., Kuller, L., Feeroz, M.M., Begum, S., Heidrich, J., and Linial, M.L. Zoonotic foamy virus infections in South Asia, Emerging Infectious Diseases, 14:1200-1208, 2008.
Life, R.B, E.-G. Lee, S.W. Eastman and and M.L.Linial. Mutations in the amino-terminus of foamy virus Gag disrupt morphology and infectivity, but not targeting of assembly. J. Virol., 82:6109-6119, 2008.