Human tissue mast cells are an inducible reservoir of persistent HIV infection.
We have proposed that, unlike other HIV-vulnerable cell lineages, progenitor mast cells (prMCs), cultured in vitro from undifferentiated bone marrow-derived CD34(+) pluripotent progenitors (PPPs), are susceptible to infection during a limited period of their ontogeny. As infected prMCs mature in culture, they lose expression of viral chemokine coreceptors necessary for viral entry and develop into long-lived, latently infected mature tissue mast cells (MCs), resistant to new infection. In vivo recruitment of prMCs to different tissue compartments occurs in response to tissue injury, growth, and remodeling or allergic inflammation, allowing populations of circulating and potentially HIV-susceptible prMCs to spread persistent infection to diverse tissue compartments. In this report, we provide in vivo evidence to confirm this model by demonstrating that HIV-infected women have both circulating prMCs and placental tissue MCs (PLMCs) that harbor inducible infectious HIV even after highly active antiretroviral therapy (HAART) during pregnancy. Furthermore, infectious virus, capable of infecting alloactivated fetal cord blood mononuclear cells (CBMCs), could be induced in isolated latently infected PLMCs after weeks in culture in vitro. These data provide the first in vivo evidence that tissue MCs, developed from infected circulating prMCs, comprise a long-lived inducible reservoir of persistent HIV in infected persons during HAART.
Sundstrom
J Bruce
JB
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. jsundst@emory.edu
Ellis
Jane E
JE
Hair
Gregory A
GA
Kirshenbaum
Arnold S
AS
Metcalfe
Dean D
DD
Yi
Hong
H
Cardona
Adriana C
AC
Lindsay
Michael K
MK
Ansari
Aftab A
AA
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000821:virology; D015658:HIV Infections / Q000473:pathology* / Q000635:transmission; D006801:Humans; D008407:Mast Cells / Q000821:virology*; D010920:Placenta / Q000821:virology; D011247:Pregnancy; D015728:Receptors, HIV / Q000032:analysis
D015728:Receptors, HIV