cytomegalovirus / herpes

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    Am J Physiol Cell Physiol. 2004 Jun 2 [Epub ahead of print]
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    Human cytomegalovirus induced host cell enlargement is iron

    Crowe WE, Maglova LM, Ponka P, Russell JM.

    Biology, Syracuse University, Syracuse, New York, USA.

    A hallmark of human cytomegalovirus (HCMV) infection is
    the characteristic enlargement of the host cells
    (cytomegaly). Since iron (Fe) is required for cell growth
    and Fe chelators will inhibit viral replication, we
    investigated the effects of HCMV infection on Fe
    homeostasis in MRC-5 fibroblasts. Using the metallo-
    sensitive fluorophore calcein and the Fe chelator
    salicylaldehyde isonicotinoyl hydrazone (SIH), the labile
    iron pool (LIP) in mock-infected cells was determined to
    be 1.04+/-0.05 micro M. Twenty-four hours post infection
    (h.p.i.), the size of the LIP was nearly doubled. Since
    cytomegaly occurs between 24 and 96 h.p.i., access to this
    larger LIP could be expected to facilitate enlargement to
    ~375% of the initial cell size. The ability of Fe
    chelation (SIH, 100 micro M) to limit enlargement to
    ~180%, confirms that the LIP plays a major role in
    cytomegaly. The effect of SIH chelation on the
    mitochondrial membrane potential (DeltaPsiM) and
    morphology was studied using the mitochondrial voltage-
    sensitive dye, JC-1. The mitochondria in mock-infected
    cells were heterogeneous with a broad distribution of
    DeltaPsiM and thread-like. In contrast, the mitochondria
    of HCMV-infected cells had a more depolarized DeltaPsiM
    distributed over a narrow range and were grain-like in
    appearance. However, the HCMV-induced alteration in
    DeltaPsiM was not affected by SIH chelation. In
    conclusion, the development of cytomegaly is inhibited by
    Fe chelation and may be facilitated by an HCMV-induced
    increase in the LIP.

    PMID: 15175225 [PubMed - as supplied by publisher]


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