Key points are not available for this paper at this time.
Retroviruses utilize cellular dNTPs to perform proviral DNA synthesis in infected host cells. Unlike oncoretroviruses, which replicate in dividing cells, lentiviruses, such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus, are capable of efficiently replicating in non-dividing cells (terminally differentiated macrophages) as well as dividing cells (i.e. activated CD4+ T cells). In general, non-dividing cells are likely to have low cellular dNTP content compared with dividing cells. Here, by employing a novel assay cellular dNTP dNTP in cells, and activated CD4+ T cells. human dNTP activated human CD4+ T cells. efficiently DNA in of low dNTP to in In with which to human activated CD4+ T cells and dividing cells. of to which to of in of to efficiently DNA synthesis in cellular dNTP Retroviruses utilize cellular dNTPs to perform proviral DNA synthesis in infected host cells. Unlike oncoretroviruses, which replicate in dividing cells, lentiviruses, such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus, are capable of efficiently replicating in non-dividing cells (terminally differentiated macrophages) as well as dividing cells (i.e. activated CD4+ T cells). In general, non-dividing cells are likely to have low cellular dNTP content compared with dividing cells. Here, by employing a novel assay cellular dNTP dNTP in cells, and activated CD4+ T cells. human dNTP activated human CD4+ T cells. efficiently DNA in of low dNTP to in In with which to human activated CD4+ T cells and dividing cells. of to which to of in of to efficiently DNA synthesis in cellular dNTP dNTP as a of cells with have dNTP in cells and are compared with cells and dividing cells have dNTP non-dividing cells dNTP and DNA and DNA synthesis are In utilize cellular dNTPs to lentiviruses, such as human and simian immunodeficiency human immunodeficiency virus type simian immunodeficiency of human immunodeficiency virus type simian immunodeficiency of and which are in to non-dividing cells, such as differentiated and dividing cells, such as activated CD4+ T cells. in and T cells of are to and of (i.e. CD4+ T and In to lentiviruses, replicate in dividing cells to DNA have to replicate efficiently in cells (i.e. macrophages) low of a dNTP assay to dNTP in host cells. efficiently DNA synthesis dNTP to in In to efficiently virus with dNTP of in cells dividing cells activated T dividing and non-dividing host cells. of to non-dividing cells in of to of dNTP DNA and of virus in virus and and DNA to DNA which of dNTP to in of with of of of with of with of and in a of and and in a dNTP assay assay of of dNTPs cellular and by in to dNTP in and with of by and of of by of in of as by assay a with which a dNTP a assay assay to of in by of and in as a of dNTP in cellular dNTPs to to dNTP in cellular by assay a assay by a to by in to and and dNTPs in in dNTP assay and as in dNTP of (i.e. 1 and and dNTPs (i.e. and in in of In with and by a of dNTP and a of with a of and and by dNTP a to a by of and dNTP of of and dNTP to a and by and and and in dNTP of in and as with and in dNTP of are as in and by and a of dNTP to a and dNTP by in and dNTP by and assay of DNA dNTP in of and and and are 1 and of DNA with are in with of human cells by human cells infected with T cells with and in with and of in CD4+ T cells and are are in cells are by cells of and and cells such cells in cells of are are with of in in of dNTP assay by to DNA of DNA with in dNTP assay as in dNTP assay DNA of dNTP to of and to of dNTP and with of and dNTPs and and with to In of dNTP in and by and dNTP cells to with and in of to cells and to and a with in dNTP and 1 cells and 1 and of dNTP of dNTP assay to of dNTP dNTP of dNTP to of In dNTP of cells dNTP content of type by and of T and and CD4+ T cells human as cells and with CD4+ by human in in human in of human and in of to T cells in with human activated T cells in with human and and in with human and human to dNTP and of and and which with in of and with by with and with and cells to with and in cells with of and of of in and and by with by of cells and of of in of and by and assay a in of and virus cells In by cells to and with which a and by with virus as by cells with compared with cells in of CD4+ T and cells and as of T with and T cells infected in of with a of of virus of of of of cells and in a of with human and and and by to by infected cells. of cells by with and in with human and by a in with human and in of with infected with virus of and 1 in of of of in and by of of with human to and cells by in by of with and of by of dNTP in and CD4+ T a dNTP assay to dNTP of and non-dividing cells such as of dNTP in a of a to of DNA dNTP assay of of DNA dNTP of efficiently low dNTP compared with of DNA and of by in of of dNTPs in of and as low as which of with and of in to of dNTP and in dNTP of dNTPs to dNTP and as in with and as well as with and dNTP to dNTP in in with of dNTPs dNTP of assay dNTP content with dNTP cells dNTP of dNTP of of dNTP content in assay and and have dNTP content in to of dNTPs as in by assay and and compared with and assay a of and of dNTPs in low dNTP of in cells dNTPs as well as which in cells with dNTPs dNTP assay by of such a of in of which to (i.e. assay by a dNTP in of and with a to (i.e. capable of dNTPs assay in of a of and dNTP dNTP assay in of dNTPs of In dNTPs to dNTPs and in cellular dNTP with of dNTP assay assay to dNTP in cells (i.e. human and activated CD4+ T cells). dNTPs cells and dNTP with as dNTP in with of in and human to and dNTPs and activated T cells, dNTP content of T cells in assay to to by assay dNTP content of human CD4+ T cells assay assay cells assay of assay of by with cellular dNTPs dNTP assay dNTP assay with dNTP of and of T of dNTP and dNTP in in with of which of with of compared with with a in with likely of in which have as in with of of and of of with of in with likely of of in of in in with of and T and 1 and of and as well as activated T cells In dNTPs with and with a of of which and T and 1 of which to to of by of with T as well as with in dNTP and of and are assay in of of cellular dNTPs and in of by cellular dNTP T cells, and in with by of in dNTP In in assay of dNTP of dNTP dNTP and with of in of to of with cellular dNTP and dNTP in dNTP content in of cellular dNTPs and have to cellular dNTP dNTP in human cells by of of human and and activated CD4+ T cells and to and which are to dNTP in human are in and activated CD4+ T cells and of dNTP in T and in to non-dividing cells such as of cells of and In and of cells dividing as by and dNTP in low a of employing and to and and and to DNA synthesis dNTP in T cells a to a compared and as of in in of and dNTP in T cells in of of dNTP (i.e. in DNA synthesis a in to of DNA synthesis with to with DNA efficiently In with and with and of dNTPs low of dNTP are of dNTP of dNTP DNA of and a of as in and a a of In and with to and by a of dNTP and in with in with with by by with and by In in as in to perform of efficiently dNTP compared with which dNTP and low dNTP assay a to a in with a dNTP low compared with to in and of dNTP DNA synthesis of and of by a dNTP assay with in and in with dNTP in and and as in dNTP to efficiently and with in in with dNTPs a in as compared with in DNA synthesis to and of and and of with dNTP to DNA efficiently in have to efficiently DNA low dNTP as in In have to efficiently DNA synthesis dNTP (i.e. are in dividing in with dNTP cellular dNTP content and of of and by to have dNTP and compared with of in dNTP of DNA by as compared with of of in dNTP (i.e. in which by to efficiently DNA low dNTP in to in to DNA synthesis low dNTP in dNTP to of likely a low dNTP DNA dNTP in by and which in dNTP dNTP a of and to by of by of with of dNTPs and a to and of in activated and T cells and are to of dNTP in cells, and (i.e. and cells, and to human T cells and in and to activated human T cells and (i.e. cellular dNTP which with of and and In and in to with of to DNA low dNTP and dNTP of a to in and to cellular dNTP and in non-dividing host cells dNTP of DNA to DNA synthesis in cellular low of dNTPs a to of to efficiently replicate in in and of of which and dNTP as a of cells with have dNTP in cells and are compared with cells and dividing cells have dNTP non-dividing cells dNTP and DNA and DNA synthesis are In utilize cellular dNTPs to lentiviruses, such as human and simian immunodeficiency human immunodeficiency virus type simian immunodeficiency of human immunodeficiency virus type simian immunodeficiency of and which are in to non-dividing cells, such as differentiated and dividing cells, such as activated CD4+ T cells. in and T cells of are to and of (i.e. CD4+ T and In to lentiviruses, replicate in dividing cells to DNA have to replicate efficiently in cells (i.e. macrophages) low of In a dNTP assay to dNTP in host cells. efficiently DNA synthesis dNTP to in In to efficiently virus with dNTP of in cells dividing cells activated T dividing and non-dividing host cells. of to non-dividing cells in of to of dNTP DNA and of virus in virus and and DNA to DNA which of dNTP to in of with of of of with of with of and in a of and and in a dNTP assay assay of of dNTPs cellular and by in to dNTP in and with of by and of of by of in of as by assay a with which a dNTP a assay assay to of in by of and in as a of dNTP in cellular dNTPs to to dNTP in cellular by assay a assay by a to by in to and and dNTPs in in dNTP assay and as in dNTP of (i.e. 1 and and dNTPs (i.e. and in in of In with and by a of dNTP and a of with a of and and by dNTP a to a by of and dNTP of human cells by human cells infected with T cells with and in with and of in CD4+ T cells and are are in cells are by cells of and and cells such cells in cells of are are with of in in of dNTP assay by to DNA of DNA with in dNTP assay as in dNTP assay DNA of dNTP to of and to of dNTP and with of and dNTPs and and with to In of dNTP in and by and dNTP cells to with and in of to cells and to and a with in dNTP and 1 cells and 1 and of dNTP of dNTP assay to of dNTP dNTP of dNTP to of In dNTP of cells dNTP content of type by and of T and and CD4+ T cells human as cells and with CD4+ by human in in human in of human and in of to T cells in with human activated T cells in with human and and in with human and human to dNTP and of and and which with in of and with by with and with and cells to with and in cells with of and of of in and and by with by of cells and of of in of and by and assay a in of and virus cells In by cells to and with which a and by with virus as by cells with compared with cells in of CD4+ T and cells and as of T with and T cells infected in of with a of of virus of of of of cells and in a of with human and and and by to by infected cells. of cells by with and in with human and by a in with human and in of with infected with virus of and 1 in of of of in and by of of with human to and cells by in by of with and of by DNA and of virus in virus and and DNA and of virus in virus and and DNA to DNA which of dNTP to in of with of of of with of with of and in a of and and in a dNTP assay assay of of dNTPs cellular and by in to dNTP in and with of by and of of by of in of as by assay a with which a dNTP a assay DNA to DNA which of dNTP to in of with of of of with of with of and in a of and and in a dNTP assay assay of of dNTPs cellular and by in to dNTP in and with of by and of of by of in of as by assay a with which a dNTP a assay assay to of in by of and in as a of dNTP in cellular dNTPs to to dNTP in cellular assay to of in by of and in as a of dNTP in cellular dNTPs to to dNTP in cellular by assay a assay by a to by in to and and dNTPs in in dNTP assay and as in dNTP of (i.e. 1 and and dNTPs (i.e. and in in of In with and by a of dNTP and a of with a of and and by dNTP a to a by of and dNTP assay a assay by a to by in to and and dNTPs in in dNTP assay and as in dNTP of (i.e. 1 and and dNTPs (i.e. and in in of In with and by a of dNTP and a of with a of and and by dNTP a to a by of and dNTP of dNTP assay by to DNA of DNA with in dNTP assay as in dNTP assay DNA of dNTP to of and to of dNTP and with of and dNTPs and and with to In of dNTP in and by and assay by to DNA of DNA with in dNTP assay as in dNTP assay DNA of dNTP to of and to of dNTP and with of and dNTPs and and with to In of dNTP in and by and dNTP dNTP cells to with and in of to cells and to and a with in dNTP and 1 cells and 1 and of dNTP of dNTP assay to of dNTP dNTP of dNTP to of In dNTP of cells dNTP content of type by dNTP cells to with and in of to cells and to and a with in dNTP and 1 cells and 1 and of dNTP of dNTP assay to of dNTP dNTP of dNTP to of In dNTP of cells dNTP content of type by and of T and and CD4+ T cells human as cells and with CD4+ by human in in human in of human and in of to T cells in with human activated T cells in with human and and in with human and human to dNTP and of and CD4+ T cells human as cells and with CD4+ by human in in human in of human and in of to T cells in with human activated T cells in with human and and in with human and human to dNTP and of and and which with in of and with by with and with and cells to with and in cells with of and of of in and and by with by of cells and of of in of and by and assay a in of and virus cells In by cells to and with which a and by with virus as by cells with compared with cells in and which with in of and with by with and with and cells to with and in cells with of and of of in and and by with by of cells and of of in of and by and assay a in of and virus cells In by cells to and with which a and by with virus as by cells with compared with cells in of CD4+ T and cells and as of T with and T cells infected in of with a of of virus of of of of cells and in a of with human and and and by to by infected cells. of cells by with and in with human and by a in with human and in of with infected with virus of and 1 in of of of in and by of of with human to and cells by in by of with and of by T cells and as T of T with and T cells infected in of with a of of virus of of of of cells and in a of with human and and and by to by infected cells. of cells by with and in with human and by a in with human and in of with infected with virus of and 1 in of of of in and by of of with human to and cells by in by of with and of by of dNTP in and CD4+ T a dNTP assay to dNTP of and non-dividing cells such as of dNTP in a of a to of DNA dNTP assay of of DNA dNTP of efficiently low dNTP compared with of DNA and of by in of of dNTPs in of and as low as which of with and of in to of dNTP and in dNTP of dNTPs to dNTP and as in with and as well as with and dNTP to dNTP in in with of dNTPs dNTP of assay dNTP content with dNTP cells dNTP of dNTP of of dNTP content in assay and and have dNTP content in to of dNTPs as in by assay and and compared with and assay a of and of dNTPs in low dNTP of in cells dNTPs as well as which in cells with dNTPs dNTP assay by of such a of in of which to (i.e. assay by a dNTP in of and with a to (i.e. capable of dNTPs assay in of a of and dNTP dNTP assay in of dNTPs of In dNTPs to dNTPs and in cellular dNTP with of dNTP assay assay to dNTP in cells (i.e. human and activated CD4+ T cells). dNTPs cells and dNTP with as dNTP in with of in and human to and dNTPs and activated T cells, dNTP content of T cells in assay to to by assay dNTP content of human CD4+ T cells assay assay cells assay of assay of by with cellular dNTPs dNTP assay dNTP assay with dNTP of and of T of dNTP and dNTP in in with of which of with of compared with with a in with likely of in which have as in with of of and of of with of in with likely of of in of in in with of and T and 1 and of and as well as activated T cells In dNTPs with and with a of of which and T and 1 of which to to of by of with T as well as with in dNTP and of and are assay in of of cellular dNTPs and in of by cellular dNTP T cells, and in with by of in dNTP In in assay of dNTP of dNTP dNTP and with of in of to of with cellular dNTP and dNTP in dNTP content in of cellular dNTPs and have to cellular dNTP dNTP in human cells by of of human and and activated CD4+ T cells and to and which are to dNTP in human are in and activated CD4+ T cells and of dNTP in T and in to non-dividing cells such as of cells of and In and of cells dividing as by and dNTP in low a of employing and to and and and to DNA synthesis dNTP in T cells a to a compared and as of in in of and dNTP in T cells in of of dNTP (i.e. in DNA synthesis a in to of DNA synthesis with to with DNA efficiently In with and with and of dNTPs low of dNTP are of dNTP of dNTP DNA of and a of as in and a a of In and with to and by a of dNTP and in with in with with by by with and by In in as in to perform of efficiently dNTP compared with which dNTP and low dNTP assay a to a in with a dNTP low compared with to in and of dNTP DNA synthesis of and of by a dNTP assay with in and in with dNTP in and and as in dNTP to efficiently and with in in with dNTPs a in as compared with in DNA synthesis to and of and and of with dNTP to DNA efficiently in have to efficiently DNA low dNTP as in In have to efficiently DNA synthesis dNTP (i.e. are in dividing in with dNTP cellular dNTP content and of of and by to have dNTP and compared with of in dNTP of DNA by as compared with of of in dNTP (i.e. in which by to efficiently DNA low dNTP in to in to DNA synthesis low dNTP in dNTP to of likely a low dNTP DNA dNTP in by and which in dNTP dNTP a to of dNTP in cells, and (i.e. and cells, and to human T cells and in and to activated human T cells and (i.e. cellular dNTP which with of and and In and in to with of to DNA low dNTP and dNTP of a to in and to cellular dNTP and in non-dividing host cells dNTP of DNA to DNA synthesis in cellular low of dNTPs a to of to efficiently replicate in in and of of which and of dNTP in and CD4+ T a dNTP assay to dNTP of and non-dividing cells such as of dNTP in a of a to of DNA dNTP assay of of DNA dNTP of efficiently low dNTP compared with of DNA and of by in of of dNTPs in of and as low as which of with and of in to of dNTP and in dNTP of dNTPs to dNTP and as in with and as well as with and dNTP to dNTP in in with of dNTPs dNTP of assay dNTP content with dNTP cells dNTP of dNTP of of dNTP content in assay and and have dNTP content in to of dNTPs as in by assay and and compared with and assay a of and of dNTPs in low dNTP of in dNTP cells dNTPs as well as which in cells with dNTPs dNTP assay by of such a of in of which to (i.e. assay by a dNTP in of and with a to (i.e. capable of dNTPs assay in of a of and dNTP dNTP assay in of dNTPs of In dNTPs to dNTPs and in cellular dNTP with of dNTP assay assay to dNTP in cells (i.e. human and activated CD4+ T cells). dNTPs cells and dNTP with as dNTP in with of in and human to and dNTPs and activated T cells, dNTP content of T cells in assay to to by assay dNTP content of human CD4+ T cells assay assay cells assay of assay of by with cellular dNTPs dNTP assay dNTP assay with dNTP of and of T of dNTP and dNTP in in with of which of with of compared with with a in with likely of in which have as in with of of and of of with of in with likely of of in of in in with of and T and 1 and of and as well as activated T cells In dNTPs with and with a of of which and T and 1 of which to to of by of with T as well as with in dNTP and of and are assay in of of cellular dNTPs and in of by cellular dNTP T cells, and in with by of in dNTP In in assay of dNTP of dNTP dNTP and with of in of to of with cellular dNTP and dNTP in dNTP content in of cellular dNTPs and have to cellular dNTP dNTP in human cells by of of human and and activated CD4+ T cells and to and which are to dNTP in human are in and activated CD4+ T cells and of dNTP in T and in to non-dividing cells such as of cells of and In and of cells dividing as by and dNTP in low a of employing and to and and and to DNA synthesis dNTP in T cells a to a compared and as of in in of and dNTP in T cells in of of dNTP (i.e. in DNA synthesis a in to of DNA synthesis with to with DNA efficiently In with and with and of dNTPs low of dNTP are of dNTP of dNTP DNA of and a of as in and a a of In and with to and by a of dNTP and in with in with with by by with and by In in as in to perform of efficiently dNTP compared with which dNTP and low dNTP assay a to a in with a dNTP low compared with to in and of dNTP DNA synthesis of and of by a dNTP assay with in and in with dNTP in and and as in dNTP to efficiently and with in in with dNTPs a in as compared with in DNA synthesis to and of and and of with dNTP to DNA efficiently in have to efficiently DNA low dNTP as in In have to efficiently DNA synthesis dNTP (i.e. are in dividing cells. in with dNTP cellular dNTP content and of of and by to have dNTP and compared with of in dNTP of DNA by as compared with of of in dNTP (i.e. in which by to efficiently DNA low dNTP in to in to DNA synthesis low dNTP in dNTP to of likely a low dNTP DNA dNTP in by and which in dNTP dNTP a to of dNTP in cells, and (i.e. and cells, and to human T cells and in and to activated human T cells and (i.e. cellular dNTP which with of and and In and in to with of to DNA low dNTP and dNTP of a to in In and to cellular dNTP and in non-dividing host cells dNTP of DNA to DNA synthesis in cellular low of dNTPs a to of to efficiently replicate in in and of of which and
Diamond et al. (Tue,) studied this question.