HIV-1 infects CD4+ T lymphocytes with a ‘helper’ function and myeloid cells, mostly tissue-resident macrophages. While infection of CD4 T lymphocytes in the absence of combination antiretroviral therapy (cART) leads to their depletion and to a profound immunodeficiency, macrophages are resistant to virus-induced cytopathicity and are a source of infectious virus, particularly in the central nervous system (CNS). Infected macrophages are characterized by accumulating newly formed viral particles (virions) in subcellular vacuoles defined as ‘virus-containing compartments (VCC)’, derived from invaginations of the plasma membrane, that are poorly accessible to antiretroviral agents and anti-HIV antibodies. Several factors favor the accumulation of HIV-1 virions in VCC in vitro, whereas extracellular ATP, via binding to its receptor P2X7, is the only agent described thus far as capable of triggering the rapid release of VCC-sequestered virions without simultaneously causing the death of infected macrophages. Thus, the eATP/P2X7 axis could be exploited to achieve a pharmacological control of VCC-associated viral reservoir in individuals under effective cART.
The ATP/P2X7 axis in human immunodeficiency virus infection of macrophages
Poli, Guido
2019-01-01
Abstract
HIV-1 infects CD4+ T lymphocytes with a ‘helper’ function and myeloid cells, mostly tissue-resident macrophages. While infection of CD4 T lymphocytes in the absence of combination antiretroviral therapy (cART) leads to their depletion and to a profound immunodeficiency, macrophages are resistant to virus-induced cytopathicity and are a source of infectious virus, particularly in the central nervous system (CNS). Infected macrophages are characterized by accumulating newly formed viral particles (virions) in subcellular vacuoles defined as ‘virus-containing compartments (VCC)’, derived from invaginations of the plasma membrane, that are poorly accessible to antiretroviral agents and anti-HIV antibodies. Several factors favor the accumulation of HIV-1 virions in VCC in vitro, whereas extracellular ATP, via binding to its receptor P2X7, is the only agent described thus far as capable of triggering the rapid release of VCC-sequestered virions without simultaneously causing the death of infected macrophages. Thus, the eATP/P2X7 axis could be exploited to achieve a pharmacological control of VCC-associated viral reservoir in individuals under effective cART.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
