(NAS Colloquium) Genetic Engineering of Viruses and Viral Vectors (1996) / Chapter Skim
Currently Skimming:
Cell-surface receptors for retroviruses and implications for gene transfer
Cell-surface receptors for retroviruses and implications for gene transfer
Pages 11407-11413
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 11407... ...
The mechanism underlying retrovirus evolution to use many receptors for cell entry is not clear, although some evidence supports a mutational model for the evolution of new receptor specificities. Further study of factors that govern retrovirus entry into cells are important for achieving high-efficiency gene transduction to specific cells and for the design of retroviral vectors to target additional receptors for cell entry.
|
From page 11408... ...
The 1041 Retrovirus Can Use Either of Two Receptors for Cell Entry Studies of cloned retrovirus receptors and most virus interference data suggested that individual retroviruses bind to a single protein for entry into cells. When different viruses bind to the same receptor, they typically show reciprocal interference; that is, infection of cells by either virus blocks entry by the other virus.
|
From page 11409... ...
Amphotropic virus can enter CHO cells expressing human or rat Raml, but not those expressing human or mouse Glvrl (data not shown j. These results explain the nonreciprocal interference observed between lOA1 and amphotropic retroviruses.
|
From page 11410... ...
For example, ecotropic retroviruses infect rodent cells, but do not infect human cells, even though human cells express a homolog of the murine ecotropic receptor that is 87% identical to the mouse protein. In this case, only two amino acid changes are required to convert the human protein into a functional receptor, or to render the mouse protein nonfunctional as an ecotropic retrovirus receptor (35, 36~.
|
From page 11411... ...
However, because Raml and Glvrl are related proteins, this change does not represent a dramatic switch in receptor specificity, and it will be interesting to see if minor amino acid changes in Env proteins can result in more dramatic changes in receptor utilization. Endogenous Synthesis of Env Protein Can Block Retrovirus Entry Retrovirus receptors can be rendered nonfunctional due to blockade by Env protein synthesized by a replicationcompetent retrovirus.
|
From page 11412... ...
Thus, subtle changes in receptor glycosylation can have a major effect on the ability of a retrovirus to utilize the receptor for cell entry. Vector Pseudotypes Available for Gene Transfer Applications Given the complicated factors that govern retrovirus entry into cells from different tissues and different species, it is helpful that there are a wide range of retrovirus packaging cell lines that are available for production of retroviral vectors with Table 6.
|
From page 11413... ...
An understanding of the principles governing cell entry by naturally occurring retroviruses will help in the design and application of these strategies. A fascinating aspect of retroviruses is their utilization of diverse proteins for cell entry.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.