This Article Full Text Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, Y. Articles by He, J. J. Search for Related Content PubMed PubMed Citation Articles by Liu, Y. Articles by He, J. J.

 Previous Article  |  Next Article 

Journal of Virology, April 2004, p. 4120-4133, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.4120-4133.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Department of Microbiology and Immunology,¹ Walther Oncology Center,² Department of Anatomy and Cell Biology,⁴ Department of Medicine, Indiana University School of Medicine,⁷ Walther Cancer Institute, Indianapolis, Indiana 46202,⁶ Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, People's Republic of China,³ Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287⁵

Received 24 September 2003/ Accepted 20 December 2003

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.

This article has been cited by other articles:

• Carroll-Anzinger, D., Kumar, A., Adarichev, V., Kashanchi, F., Al-Harthi, L. (2007). Human Immunodeficiency Virus-Restricted Replication in Astrocytes and the Ability of Gamma Interferon To Modulate This Restriction Are Regulated by a Downstream Effector of the Wnt Signaling Pathway. J. Virol. 81: 5864-5871 [Abstract] [Full Text]  
• Trujillo, J. R., Rogers, R., Molina, R. M., Dangond, F., McLane, M. F., Essex, M., Brain, J. D. (2007). Noninfectious entry of HIV-1 into peripheral and brain macrophages mediated by the mannose receptor. Proc. Natl. Acad. Sci. USA 104: 5097-5102 [Abstract] [Full Text]  
• Hill, M. S., Ruiz, A., Gomez, L. M., Miller, J.-M., Berman, N. E.J., Stephens, E. B. (2007). APOBEC3G Expression Is Restricted to Epithelial Cells of the Proximal Convoluted Tubules and Is Not Expressed in the Glomeruli of Macaques. J. Histochem. Cytochem. 55: 63-70 [Abstract] [Full Text]  
• Ronaldson, P. T., Bendayan, R. (2006). HIV-1 Viral Envelope Glycoprotein gp120 Triggers an Inflammatory Response in Cultured Rat Astrocytes and Regulates the Functional Expression of P-Glycoprotein. Mol. Pharmacol. 70: 1087-1098 [Abstract] [Full Text]  
• Zhang, P., Schwartz, O., Pantelic, M., Li, G., Knazze, Q., Nobile, C., Radovich, M., He, J., Hong, S.-C., Klena, J., Chen, T. (2006). DC-SIGN (CD209) recognition of Neisseria gonorrhoeae is circumvented by lipooligosaccharide variation. J. Leukoc. Biol. 79: 731-738 [Abstract] [Full Text]  
• Carroll-Anzinger, D., Al-Harthi, L. (2006). Gamma Interferon Primes Productive Human Immunodeficiency Virus Infection in Astrocytes. J. Virol. 80: 541-544 [Abstract] [Full Text]  
• Vidricaire, G., Tremblay, M. J. (2005). Rab5 and Rab7, but Not ARF6, Govern the Early Events of HIV-1 Infection in Polarized Human Placental Cells. J. Immunol. 175: 6517-6530 [Abstract] [Full Text]  
• Sancho, R., de la Vega, L., Macho, A., Appendino, G., Di Marzo, V., Munoz, E. (2005). Mechanisms of HIV-1 Inhibition by the Lipid Mediator N-Arachidonoyldopamine. J. Immunol. 175: 3990-3999 [Abstract] [Full Text]  
• Neil, S. J. D., Aasa-Chapman, M. M. I., Clapham, P. R., Nibbs, R. J., McKnight, A., Weiss, R. A. (2005). The Promiscuous CC Chemokine Receptor D6 Is a Functional Coreceptor for Primary Isolates of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 on Astrocytes. J. Virol. 79: 9618-9624 [Abstract] [Full Text]  
• Vigerust, D. J., Egan, B. S., Shepherd, V. L. (2005). HIV-1 Nef mediates post-translational down-regulation and redistribution of the mannose receptor. J. Leukoc. Biol. 77: 522-534 [Abstract] [Full Text]