HIV-1-infected astrocytes and the microglial proteome.
The human immunodeficiency virus (HIV) invades the central nervous system early after viral exposure but causes progressive cognitive, behavior, and motor impairments years later with the onset of immune deficiency. Although in the brain, HIV preferentially replicates productively in cells of mononuclear phagocyte (MP; blood borne macrophage and microglia), astrocytes also can be infected, at low and variable frequency, particularly in patients with encephalitis. Among their many functions, astrocytes network with microglia to provide the first line of defense against microbial infection; however, very little is known about astrocytes' consequences on MP. Here, we addressed this question using co-culture systems of HIV-infected mouse astrocytes and microglia. Pseudotyped vesicular stomatis virus/HIV was used to circumvent the absence of viral receptors and ensure cell genotypic uniformity for studies of intercellular communication. The study demonstrated that infected astrocytes show modest changes in protein elements compared to uninfected cells. In contrast, infected astrocytes induce robust changes in the proteome of HIV-1-infected microglia. Accelerated cell death and redox proteins, among others, were produced in abundance. The observations confirmed the potential of astrocytes to influence the neuropathogenesis of HIV-1 infection by specifically altering the neurotoxic potential of infected microglia and regulating viral maturation.
Wang
Tong
T
Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Gong
Nan
N
Liu
Jianuo
J
Kadiu
Irena
I
Kraft-Terry
Stephanie D
SD
Schlautman
Joshua D
JD
Ciborowski
Pawel
P
Volsky
David J
DJ
Gendelman
Howard E
HE
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology / Q000821:virology; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000473:pathology* / Q000821:virology*; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000737:chemistry / Q000473:pathology* / Q000821:virology*; D011247:Pregnancy; D020543:Proteome / Q000096:biosynthesis* / Q000235:genetics
D020543:Proteome