Abstract
Viruses interact with various permissive and restrictive factors in host cells throughout their replication cycle. Cell lines that are non-permissive to viral infection have been particularly useful in discovering host cell proteins involved in viral life cycles. Here we describe the characterization of a human myeloid leukemia cell line, KG-1, that is resistant to infection by retroviruses and a Rhabdovirus. We show that KG-1 cells are resistant to infection by Vesicular Stomatits Virus as well as VSV Glycoprotein (VSVG) pseudotyped retroviruses due to a defect in binding. Moreover our results indicate that entry by xenotropic retroviral envelope glycoprotein RD114 is impaired in KG-1 cells. Finally we characterize a post- entry block in the early phase of the retroviral life cycle in KG-1 cells that renders the cell line refractory to infection. This cell line will have utility in discovering proteins involved in infection by VSV and HIV-1.
Highlights
As obligate intracellular pathogens retroviruses are intimately dependent on host cell factors throughout their life cycle
First we infected KG-1 cells with HIV-Vesicular Stomatitis Virus (VSV) Glycoprotein (VSVG) at higher multiplicities block is unique to HIV-1 we used another retroviral vector based on a gammaretrovirus Murine Leukemia Virus (MLV)
These results indicate that KG-1 cells are resistant to VSVG pseudotyped retroviral vectors
Summary
As obligate intracellular pathogens retroviruses are intimately dependent on host cell factors throughout their life cycle. In addition to the cellular cofactors that are exploited by viruses several cellular proteins (restriction factors) have been found to act in an inhibitory role to combat viral infection. Various methods have been used to identify cofactors and restriction factors including genome wide RNAi screening (see for examples [1] and [2]), analyses of host proteins that interact with specific viral proteins Our laboratory as well as other groups previously isolated mammalian cell lines resistant to infection by retroviruses using loss-of-function genetic screens [7], [8]. Characterization of some of these cell lines led to identification of multiple host factors that are involved in retroviral infection such as Zinc Finger Antiviral Protein and fasciculation elongation protein zeta-1 [9]. Gain-of-function genetic screens have helped identify viral co-factors.
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