Macrophages archive HIV-1 virions for dissemination in trans.
Viruses have evolved various strategies in order to persist within the host. To date, most information on mechanisms of HIV-1 persistence has been derived from studies with lymphocytes, but there is little information regarding mechanisms that govern HIV-1 persistence in macrophages. It has previously been demonstrated that virus assembly in macrophages occurs in cytoplasmic vesicles, which exhibit the characteristics of multivesicular bodies or late endosomes. The infectious stability of virions that assemble intracellularly in macrophages has not been evaluated. We demonstrate that virions assembling intracellularly in primary macrophages retain infectivity for extended intervals. Infectious virus was recovered directly from cytoplasmic lysates of macrophages and could be transmitted from macrophages to peripheral blood lymphocytes in trans 6 weeks after ongoing viral replication was blocked. Cell-associated virus decayed significantly from 1 to 2 weeks post infection, but decreased minimally thereafter. The persistence of intracellular virions did not require the viral accessory proteins Vpu or Nef. The stable sequestration of infectious virions within cytoplasmic compartments of macrophages may represent an additional mechanism for viral persistence in HIV-1-infected individuals.
Sharova
Natalia
N
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Swingler
Catherine
C
Sharkey
Mark
M
Stevenson
Mario
M
D002478:Cells, Cultured; D015693:Gene Products, nef / Q000502:physiology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D046529:Microscopy, Electron, Transmission; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology; D014771:Virion / Q000502:physiology*; D019065:Virus Assembly; D054311:nef Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
D015693:Gene Products, nef; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins