Previous Article | Next Article 
Journal of Virology, October 2005, p. 12132-12147, Vol. 79, No. 19
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.19.12132-12147.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Stoichiometry of Envelope Glycoprotein Trimers in the Entry of Human Immunodeficiency Virus Type 1
Xinzhen Yang,1,2*
Svetla Kurteva,1
Xinping Ren,1,2
Sandra Lee,3,4 and
Joseph Sodroski1,2,5
Department of Cancer Immunology and AIDS,1
Department of Biostatistical Science, Dana-Farber Cancer Institute,3
Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,2
Department of Biostatistics,4
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 021155
Received 24 March 2005/
Accepted 5 July 2005
The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Envs) function as a trimer, mediating virus entry by promoting the fusion of the viral and target cell membranes. HIV-1 Env trimers induce membrane fusion through a pH-independent pathway driven by the interaction between an Env trimer and its cellular receptors, CD4 and CCR5/CXCR4. We studied viruses with mixed heterotrimers of wild-type and dominant-negative Envs to determine the number (T) of Env trimers required for HIV-1 entry. To our surprise, we found that a single Env trimer is capable of supporting HIV-1 entry; i.e., T = 1. A similar approach was applied to investigate the entry stoichiometry of envelope glycoproteins from amphotropic murine leukemia virus (A-MLV), avian sarcoma/leukosis virus type A (ASLV-A), and influenza A virus. When pseudotyped on HIV-1 virions, the A-MLV and ASLV-A Envs also exhibit a T = 1 entry stoichiometry. In contrast, eight to nine influenza A virus hemagglutinin trimers function cooperatively to achieve membrane fusion and virus entry, using a pH-dependent pathway. The different entry requirements for cooperativity among Env trimers for retroviruses and influenza A virus may influence viral strategies for replication and evasion of the immune system.
* Corresponding author. Mailing address: Dana-Farber Cancer Institute, Department of Cancer Immunology and AIDS, 44 Binney Street, JFB 824, Boston, MA 02115. Phone: (617) 632-4359. Fax: (617) 632-4338. E-mail:
xinzhen_yang{at}dfci.harvard.edu.
Journal of Virology, October 2005, p. 12132-12147, Vol. 79, No. 19
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.19.12132-12147.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Le Duff, Y., Blanchet, M., Sureau, C.
(2009). The Pre-S1 and Antigenic Loop Infectivity Determinants of the Hepatitis B Virus Envelope Proteins Are Functionally Independent. J. Virol.
83: 12443-12451
[Abstract]
[Full Text]
-
Bryson, S., Julien, J.-P., Hynes, R. C., Pai, E. F.
(2009). Crystallographic Definition of the Epitope Promiscuity of the Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5: Vaccine Design Implications. J. Virol.
83: 11862-11875
[Abstract]
[Full Text]
-
Magnus, C., Rusert, P., Bonhoeffer, S., Trkola, A., Regoes, R. R.
(2009). Estimating the Stoichiometry of Human Immunodeficiency Virus Entry. J. Virol.
83: 1523-1531
[Abstract]
[Full Text]
-
Barcena, M., Oostergetel, G. T., Bartelink, W., Faas, F. G. A., Verkleij, A., Rottier, P. J. M., Koster, A. J., Bosch, B. J.
(2009). Cryo-electron tomography of mouse hepatitis virus: Insights into the structure of the coronavirion. Proc. Natl. Acad. Sci. USA
106: 582-587
[Abstract]
[Full Text]
-
Dobrowsky, T. M., Zhou, Y., Sun, S. X., Siliciano, R. F., Wirtz, D.
(2008). Monitoring Early Fusion Dynamics of Human Immunodeficiency Virus Type 1 at Single-Molecule Resolution. J. Virol.
82: 7022-7033
[Abstract]
[Full Text]
-
Huang, I-C., Li, W., Sui, J., Marasco, W., Choe, H., Farzan, M.
(2008). Influenza A Virus Neuraminidase Limits Viral Superinfection. J. Virol.
82: 4834-4843
[Abstract]
[Full Text]
-
Blay, W. M., Kasprzyk, T., Misher, L., Richardson, B. A., Haigwood, N. L.
(2007). Mutations in Envelope gp120 Can Impact Proteolytic Processing of the gp160 Precursor and Thereby Affect Neutralization Sensitivity of Human Immunodeficiency Virus Type 1 Pseudoviruses. J. Virol.
81: 13037-13049
[Abstract]
[Full Text]
-
Jiang, J., Aiken, C.
(2007). Maturation-Dependent Human Immunodeficiency Virus Type 1 Particle Fusion Requires a Carboxyl-Terminal Region of the gp41 Cytoplasmic Tail. J. Virol.
81: 9999-10008
[Abstract]
[Full Text]
-
Yang, X., Lipchina, I., Lifton, M., Wang, L., Sodroski, J.
(2007). Antibody Binding in Proximity to the Receptor/Glycoprotein Complex Leads to a Basal Level of Virus Neutralization. J. Virol.
81: 8809-8813
[Abstract]
[Full Text]
-
Bellamy-McIntyre, A. K., Lay, C.-S., Baar, S., Maerz, A. L., Talbo, G. H., Drummer, H. E., Poumbourios, P.
(2007). Functional Links between the Fusion Peptide-proximal Polar Segment and Membrane-proximal Region of Human Immunodeficiency Virus gp41 in Distinct Phases of Membrane Fusion. J. Biol. Chem.
282: 23104-23116
[Abstract]
[Full Text]
-
Garg, H., Joshi, A., Freed, E. O., Blumenthal, R.
(2007). Site-specific Mutations in HIV-1 gp41 Reveal a Correlation between HIV-1-mediated Bystander Apoptosis and Fusion/Hemifusion. J. Biol. Chem.
282: 16899-16906
[Abstract]
[Full Text]
-
Haim, H., Steiner, I., Panet, A.
(2007). Time Frames for Neutralization during the Human Immunodeficiency Virus Type 1 Entry Phase, as Monitored in Synchronously Infected Cell Cultures. J. Virol.
81: 3525-3534
[Abstract]
[Full Text]
-
Alfadhli, A., Huseby, D., Kapit, E., Colman, D., Barklis, E.
(2007). Human Immunodeficiency Virus Type 1 Matrix Protein Assembles on Membranes as a Hexamer. J. Virol.
81: 1472-1478
[Abstract]
[Full Text]
-
Lambele, M., Labrosse, B., Roch, E., Moreau, A., Verrier, B., Barin, F., Roingeard, P., Mammano, F., Brand, D.
(2007). Impact of Natural Polymorphism within the gp41 Cytoplasmic Tail of Human Immunodeficiency Virus Type 1 on the Intracellular Distribution of Envelope Glycoproteins and Viral Assembly. J. Virol.
81: 125-140
[Abstract]
[Full Text]
-
Imai, M., Mizuno, T., Kawasaki, K.
(2006). Membrane Fusion by Single Influenza Hemagglutinin Trimers: KINETIC EVIDENCE FROM IMAGE ANALYSIS OF HEMAGGLUTININ-RECONSTITUTED VESICLES. J. Biol. Chem.
281: 12729-12735
[Abstract]
[Full Text]
-
Yang, X., Kurteva, S., Ren, X., Lee, S., Sodroski, J.
(2006). Subunit Stoichiometry of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers during Virus Entry into Host Cells. J. Virol.
80: 4388-4395
[Abstract]
[Full Text]
-
Tscherne, D. M., Jones, C. T., Evans, M. J., Lindenbach, B. D., McKeating, J. A., Rice, C. M.
(2006). Time- and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry. J. Virol.
80: 1734-1741
[Abstract]
[Full Text]