CD4-Independent Infection of Astrocytes by Human Immunodeficiency Virus Type 1: Requirement for the Human Mannose Receptor

Ying Liu, Hao Liu, Byung Oh Kim, Vincent H. Gattone, Jinliang Li, Avindra Nath, Janice Blum, Johnny J. He

Research output: Contribution to journalArticle

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection occurs in the central nervous system and causes a variety of neurobehavioral and neuropathological disorders. Both microglia, the residential macrophages in the brain, and astrocytes are susceptible to HIV-1 infection. Unlike microglia that express and utilize CD4 and chemokine coreceptors CCR5 and CCR3 for HIV-1 infection, astrocytes fail to express CD4. Astrocytes express several chemokine coreceptors; however, the involvement of these receptors in astrocyte HIV-1 infection appears to be insignificant. In the present study using an expression cloning strategy, the cDNA for the human mannose receptor (hMR) was found to be essential for CD4-independent HIV-1 infectivity. Ectopic expression of functional hMR rendered U87.MG astrocytic cells susceptible to HIV-1 infection, whereas anti-hMR serum and hMR-specific siRNA blocked HIV-1 infection in human primary astrocytes. In agreement with these findings, hMR bound to HIV-1 virions via the abundant and highly mannosylated sugar moieties of HIV-1 envelope glycoprotein gp120 in a Ca2+-dependent fashion. Moreover, hMR-mediated HIV-1 infection was dependent upon endocytic trafficking as assessed by transmission electron microscopy, as well as inhibition of viral entry by endosomo- and lysosomotropic drugs. Taken together, these results demonstrate the direct involvement of hMR in HIV-1 infection of astrocytes and suggest that HIV-1 interaction with hMR plays an important role in HIV-1 neuropathogenesis.

Original languageEnglish (US)
Pages (from-to)4120-4133
Number of pages14
JournalJournal of Virology
Volume78
Issue number8
DOIs
StatePublished - Apr 2004

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astrocytes
Human immunodeficiency virus 1
mannose
Astrocytes
HIV-1
Virus Diseases
receptors
Infection
infection
neuroglia
Microglia
chemokines
Chemokines
mannose receptor
small interfering RNA
Transmission Electron Microscopy
virion
Virion
Small Interfering RNA
central nervous system

ASJC Scopus subject areas

  • Immunology

Cite this

CD4-Independent Infection of Astrocytes by Human Immunodeficiency Virus Type 1 : Requirement for the Human Mannose Receptor. / Liu, Ying; Liu, Hao; Kim, Byung Oh; Gattone, Vincent H.; Li, Jinliang; Nath, Avindra; Blum, Janice; He, Johnny J.

In: Journal of Virology, Vol. 78, No. 8, 04.2004, p. 4120-4133.

Research output: Contribution to journalArticle

Liu, Ying ; Liu, Hao ; Kim, Byung Oh ; Gattone, Vincent H. ; Li, Jinliang ; Nath, Avindra ; Blum, Janice ; He, Johnny J. / CD4-Independent Infection of Astrocytes by Human Immunodeficiency Virus Type 1 : Requirement for the Human Mannose Receptor. In: Journal of Virology. 2004 ; Vol. 78, No. 8. pp. 4120-4133.
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