Christine A. Kozak, Ph.D.

Chief, Viral Biology Section

Christine Kozak received her Ph.D. from Yale University and her B.A. from Emmanuel College. After a postdoctoral fellowship at NIAID under Wallace Rowe, she joined the Laboratory of Molecular Microbiology in 1984. She has served on the Committee on Standardized Nomenclature for Mice and was chair of the Mouse Chromosome 5 Committee for 10 years.

Description of Research Program

The Viral Biology Section has a longstanding interest in genes responsible for resistance to mouse leukemia viruses (MLVs) and to the diseases these viruses induce. We are particularly interested in those genes that specifically affect the viral replicative cycle. Although some of these genes, like Fv1, have been cloned, the underlying molecular mechanisms responsible for these resistance phenotypes are largely unknown. For these studies, we use wild mouse species as well as laboratory strains because the common inbred strains were all derived from the same common progenitors and are therefore not representative of the range of genetic diversity within Mus. Our active projects focus on five different resistance genes (Fv1, Rmcf, Rmcf2, Lvif, Rmc1). Additional projects are focused on unusual infectious viruses isolated from wild mouse species.

Recent Data

1. Determination that substitutions of two different amino acid residues within the virus capsid gene are responsible for two Fv1-mediated tropism variants
2. Demonstration that the serum factor that inactivates some MLVs is produced by a gene on mouse Chr 10
3. Identification of proviral sequences integrated at the chromosomal loci that govern resistance at Rmcf and Rmcf2
4. Demonstration that Mus castaneus mice are resistant to some MLVs because they carry a defective Rmc1 receptor gene
5. Demonstration that some wild mouse species contain proviral sequences that can contribute to the generation of infectious virus
6. Isolation of two MLVs with different amino acid substitutions at the same site within the viral envelope gene that induces the formation of large multinucleated syncytia in cells carrying variant receptors (Figure 1)

Figure 1: Cells infected by a virus isolated from Mus spicilegus.

Editorial Boards

• Journal of Heredity
• Mammalian Genome
• Genomics

Research Group Members

Esther Shaffer, Biologist, eshaffer@niaid.nih.gov; Yuhe Yan, Ph.D., Visiting Fellow, yyan@niaid.nih.gov.

Selected Publications

(View list in PubMed.)

Wu T, Yan Y, Kozak CA. Rmcf2, a xenotropic provirus in the Asian mouse species Mus castaneus, blocks infection by polytropic mouse gammaretroviruses. J Virol. 2005. 79(15): 9677-9684.

Jung YT, Wu T, Kozak CA. Novel host range and cytopathic variant of ecotropic Friend murine leukemia virus. J Virol. 2004 Nov;78(22): 12189-12197.

Jung YT, Wu T, Kozak CA. Characterization of recombinant nonecotropic murine leukemia viruses from the wild mouse species Mus spretus. J Virol. 2003. 77(23): 12773-12781.

Jung YT, Kozak CA. Generation of novel syncytium-inducing and host range variants of ecotropic moloney murine leukemia virus in Mus spicilegus. J Virol. 2003. 77(9): 5065-5072.

Denicourt C, Kozak CA. Rassart EGris1, a new common integration site in Graffi murine leukemia virus-induced leukemias: overexpression of a truncated cyclin D2 due to alternative splicing. J Virol. 2003. 77(1): 37-44.

Jung YT, Lyu MS, Buckler-White A, Kozak CA. Characterization of a polytropic murine leukemia virus proviral sequence associated with the virus resistance gene Rmcf of DBA/2 mice. J Virol. 2002. 76(16): 8218-8224.

Genetics special interest group
Virology special interest group

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