Human immunodeficiency virus infection of T-lymphoblastoid cells reduces intracellular pH.
Alterations in plasma membrane function are induced by many cytopathic viruses, including human immunodeficiency virus type 1 (HIV-1). These alterations can result in changes in the intracellular content of ions and other small molecules and can contribute to cytolysis and death of the infected cell. The pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein-acetoxymethyl ester was used to quantitate intracellular pH (pHi) in HIV-1-infected T cells. Infection of cells from the CD4+ T-lymphoblastoid line HUT-78 (RH9 subclone) with HIV-1 strain LAI resulted in a significant decrease of pHi, from approximately 7.2 in mock-infected cells to below 6.7 by day 4 after infection, when cells were undergoing acute cytopathic effects. The pHi in persistently infected cells that survived the acute cytopathic effects of HIV-1 was approximately 6.8 to 7.0. Studies with amiloride, an inhibitor of the Na+/H+ exchange system, suggest that HIV-1-induced intracellular acidification in lymphocytes is due, in part, to dysfunction of this plasma membrane ion transport system. The alterations in pHi may mediate certain cytopathic effects of HIV-1, thereby contributing to depletion of CD4+ T lymphocytes in patients with AIDS.
Makutonina
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A
Graduate Program in Molecular and Cellular Biology, Tulane University, New Orleans, Louisiana 70112, USA.
Voss
T G
TG
Plymale
D R
DR
Fermin
C D
CD
Norris
C H
CH
Vigh
S
S
Garry
R F
RF
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000821:virology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport