Fred Hutchinson Cancer Research Center Basic Sciences Division MemberAppointed: 1983 University of Washington Public Health Pathobiology Research ProfessorAppointed: 2002 Fred Hutchinson Cancer Research Center Basic Sciences Division Interdisciplinary Research Training Appointed: 1998 University of Washington School of Medicine Microbiology Research ProfessorAppointed: 1988 |  |
QualificationsB.S., Tufts University, Bacteriology. Ph.D., Tufts University, Microbiology and Molecular Biology. Expertise and Research InterestsOur 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 zoonotic infections.
Foamy viruses 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.
We have been studying how FV can establish life long persistent infections without ensuing pathology. Using naturally infected rhesus macaques, we have found that viral replication is confined to tissues of the oral mucosa. Recently, we have shown that superficial epithelial cells, destined to be sloughed into saliva, are the in vivo target cells for FV replication. This limited niche can explain the lack of viral pathology, and the efficient transmission through saliva.
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. Other ExpertiseAcademic Experience: Editorial Board of "Virology" Editorial Board of "Journal of Virology" KeywordsCOS Keywords:Genetics, Microbiology, Molecular Biology, Pathobiology, Retrovirus, Tissue Culture, Viral Infections, Virology.Additional Terms:Genetics, Microbiology, Molecular Biology, Viral Disease, Viral Replication, Viruses.MembershipsAmerican Association for the Advancement of Science American Society for Microbiology American Society for Virology Publications- Roy, J,, Linial, M.L. (2007) Role of the foamy virus Pol cleavage site in viral replication, Journal of Virology, 81, 4956-4962
- Jones-Engel, L., Steinkraus, K.A., Murray, S.M., Engel, G.A., Grant, R, Aggimarangsee, N., Lee, B.P,Y-H, May, C, Schillaci, M.A., Somgird, C, Sutthipat, T, Vojtech, L, Zhao, J-Y., Linial, M.L. (2007) Sensitive assays for simian foamy viruses reveal a high prevalence of infection in commensal, free-ranging, Asian monkeys, Journal of Virology, 81, 7330-7337
- Linial, M.L. (2007) Ch. 61:Foamy Viruses, Fields Virology, 5th Edition, Philadelphia, Lippincott Williams & Wilkins, 2245-2262 pages (bookchapter)
- Murray, S.M. (2006) Expanded tissue targets for foamy virus replication with SIV induced immunosuppression, Journal of Virology, 80, 663-670
- Yu, S.F. (2006) Foamy virus capsid assembly occurs at a pericentriolar region through a cytoplasmic/targeting retention signal in Gag, Traffic, 7, 966-977
- Duda A, Stange A, Luftenegger D, Stanke N, Westphal D, Pietschmann T, Eastman SW, Linial ML, Rethwilm A, Lindemann D (2004) Prototype foamy virus envelope glycoprotein leader peptide processing is, Journal of Virology, 78 (24), 13865-70
 - Lee EG, Linial ML, Basic residues of the retroviral nucleocapsid play different roles in
gag-gag and Gag-Psi RNA interactions, Journal of Virology, 78(16), 8486-95, August 2004
 - Boyer PL, Stenbak CR, Clark PK, Linial ML, Hughes SH, Characterization of the polymerase and RNase H activities of human foamy
virus reverse transcriptase, Journal of Virology, 78(12), 6112-21, June 2004
 - Stenbak CR, Linial ML (Sep 2004) Role of the C terminus of foamy virus Gag in RNA packaging and Pol, Journal of Virology, 78 (17), 9423-30
 - Meiering CD, Linial ML, The promyelocytic leukemia protein does not mediate foamy virus latency in
vitro, Journal of Virology, 77(3), 2207-13, February 2003
 - Lee EG, Alidina A, May C, Linial ML, Importance of basic residues in binding of Rous sarcoma virus nucleocapsid, Journal of Virology, 77(3), 2010-20, February 2003
 - Rinke CS, Boyer PL, Sullivan MD, Hughes SH, Linial ML, Mutation of the catalytic domain of the foamy virus reverse transcriptase
leads to loss of processivity and infectivity, Journal of Virology, 76(15), 7560-70, Aug 2002
 - Meiering, C.D, Linial, M.L., Reactivation of a complex retrovirus is controlled by a molecular switch and is inhibited by a viral protein, Proceedings of the National Academy of Sciences (USA), 99:, 15130-15135, 2002
- Eastman SW, Linial ML, Identification of a conserved residue of foamy virus Gag required for
intracellular capsid assembly, Journal of Virology, 75(15), 6857-64, August 2001
 - Meiering CD, Rubio C, May C, Linial ML, Cell-type-specific regulation of the two foamy virus promoters, Journal of Virology, 75(14), 6547-57, July 2001
 - Meiering CD, Linial ML, Historical perspective of foamy virus epidemiology and infection, Clinical Microbiology Reviews, 14(1), 165-76, Jan 2001
 - Lee, E-.G, Linial, M.L., Yeast three-hybrid screening of Rous sarcoma virus mutants with randomly mutagenized minimal packaging signals reveals regions important for Gag interactions, Journal of Virology, 74(19), 9167-9174, October 2000
- Meiering CD, Comstock KE, Linial ML, Multiple integrations of human foamy virus in persistently infected human erythroleukemia cells, Journal of Virology, 74(4), 1718-26, February 2000
 - Banks JD, Linial ML, Secondary structure analysis of a minimal avian leukosis-sarcoma virus packaging signal, Journal of Virology, 74(1), 456-64, Jan 2000
 - Linial, M.L., Why aren't foamy viruses pathogenic?, Trends in Microbiology, 8, 284-289, 2000
- Baldwin DN, Linial ML, Proteolytic activity, the carboxy terminus of Gag, and the primer binding site are not required for Pol incorporation into foamy virus particles, Journal of Virology, 73(8), 6387-93, August 1999
 - Lee E.-G., Yeo A, Kraemer B, Wickens M, Linial ML, The gag domains required for avian retroviral RNA encapsidation determined by using two independent assays, Journal of Virology, 73(8), 6282-92, August 1999
- Linial ML, Foamy viruses are unconventional retroviruses, Journal of Virology, 73(3), 1747-55, March 1999

Profile DetailsIndividual Expertise profile of Maxine L. Linial, Copyright Maxine L. Linial. © COS Expertise TM, 2008, ProQuest LLC All rights reserved. |