Previous Article | Next Article 
J Virol, August 1998, p. 6520-6526, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
In Vivo Pathogenesis of a Human Immunodeficiency
Virus Type 1 Reporter Virus
Beth D.
Jamieson1 and
Jerome A.
Zack1,2,*
Division of Hematology-Oncology, Department
of Medicine,1 and
Department of
Microbiology and Molecular Genetics,2 UCLA
School of Medicine and UCLA AIDS Institute, Los Angeles, California
90095-1678
Received 5 March 1998/Accepted 12 May 1998
Our understanding of human immunodeficiency virus type 1 (HIV-1)-induced pathogenesis is hampered by the inability to detect HIV-1 gene expression in infected viable cells. In this report, we
describe two HIV-1 reporter constructs that are replication competent
and cytopathic in vivo. These constructs contain DNA regions of two
different lengths that bear the cDNA for the murine heat-stable antigen
in the vpr region of a CXCR4-tropic virus. We used the
SCID-hu mouse model and these reporter viruses to perform detailed
kinetic studies of HIV-1 infection of human thymocytes in vivo. We
document that the CD4+/CD8+ thymocytes are the
first to express virus and that this subset demonstrates the most rapid
and extensive HIV-1-induced cell depletion. Following depletion of this
subset, subsequent virus expression occurs predominantly in
phenotypically CD4
cells, suggesting that CD4
down-regulation occurs in HIV-1-infected thymocytes in vivo. These
results demonstrate the utility of these HIV-1 reporter constructs to
monitor HIV pathogenesis in vitro and in vivo.
*
Corresponding author. Mailing address: Departments of
Medicine and Microbiology and Molecular Genetics, UCLA School of
Medicine and UCLA AIDS Institute, 11-934 Factor Bldg., Box 951678, Los Angeles, CA 90095-1678. Phone: (310) 794-7765. Fax: (310) 825-6192. E-mail: jzack{at}ucla.edu.
J Virol, August 1998, p. 6520-6526, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Muthumani, K., Choo, A. Y., Shedlock, D. J., Laddy, D. J., Sundaram, S. G., Hirao, L., Wu, L., Thieu, K. P., Chung, C. W., Lankaraman, K. M., Tebas, P., Silvestri, G., Weiner, D. B.
(2008). Human Immunodeficiency Virus Type 1 Nef Induces Programmed Death 1 Expression through a p38 Mitogen-Activated Protein Kinase-Dependent Mechanism. J. Virol.
82: 11536-11544
[Abstract]
[Full Text]
-
Roth, M. D., Whittaker, K. M., Choi, R., Tashkin, D. P., Baldwin, G. C.
(2005). Cocaine and {sigma}-1 receptors modulate HIV infection, chemokine receptors, and the HPA axis in the huPBL-SCID model. J. Leukoc. Biol.
78: 1198-1203
[Abstract]
[Full Text]
-
Clay, C. C., Rodrigues, D. S., Harvey, D. J., Leutenegger, C. M., Esser, U.
(2005). Distinct Chemokine Triggers and In Vivo Migratory Paths of Fluorescein Dye-Labeled T Lymphocytes in Acutely Simian Immunodeficiency Virus SIVmac251-Infected and Uninfected Macaques. J. Virol.
79: 13759-13768
[Abstract]
[Full Text]
-
Choi, J., Walker, J., Talbert-Slagle, K., Wright, P., Pober, J. S., Alexander, L.
(2005). Endothelial Cells Promote Human Immunodeficiency Virus Replication in Nondividing Memory T Cells via Nef-, Vpr-, and T-Cell Receptor-Dependent Activation of NFAT. J. Virol.
79: 11194-11204
[Abstract]
[Full Text]
-
Brown, A., Gartner, S., Kawano, T., Benoit, N., Cheng-Mayer, C.
(2005). HLA-A2 down-regulation on primary human macrophages infected with an M-tropic EGFP-tagged HIV-1 reporter virus. J. Leukoc. Biol.
78: 675-685
[Abstract]
[Full Text]
-
Choudhary, S. K., Choudhary, N. R., Kimbrell, K. C., Colasanti, J., Ziogas, A., Kwa, D., Schuitemaker, H., Camerini, D.
(2005). R5 Human Immunodeficiency Virus Type 1 Infection of Fetal Thymic Organ Culture Induces Cytokine and CCR5 Expression. J. Virol.
79: 458-471
[Abstract]
[Full Text]
-
Koka, P. S., Kitchen, C. M. R., Reddy, S. T.
(2004). Targeting c-Mpl for Revival of Human Immunodeficiency Virus Type 1-Induced Hematopoietic Inhibition When CD34+ Progenitor Cells Are Re-Engrafted into a Fresh Stromal Microenvironment In Vivo. J. Virol.
78: 11385-11392
[Abstract]
[Full Text]
-
Bahbouhi, B., Landay, A., Al-Harthi, L.
(2004). Dynamics of cytokine expression in HIV productively infected primary CD4+ T cells. Blood
103: 4581-4587
[Abstract]
[Full Text]
-
Ali, A., Lubong, R., Ng, H., Brooks, D. G., Zack, J. A., Yang, O. O.
(2004). Impacts of Epitope Expression Kinetics and Class I Downregulation on the Antiviral Activity of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes. J. Virol.
78: 561-567
[Abstract]
[Full Text]
-
Brooks, D. G., Arlen, P. A., Gao, L., Kitchen, C. M. R., Zack, J. A.
(2003). Identification of T cell-signaling pathways that stimulate latent HIV in primary cells. Proc. Natl. Acad. Sci. USA
100: 12955-12960
[Abstract]
[Full Text]
-
Ali, A., Pillai, S., Ng, H., Lubong, R., Richman, D. D., Jamieson, B. D., Ding, Y., McElrath, M. J., Guatelli, J. C., Yang, O. O.
(2003). Broadly Increased Sensitivity to Cytotoxic T Lymphocytes Resulting from Nef Epitope Escape Mutations. J. Immunol.
171: 3999-4005
[Abstract]
[Full Text]
-
Qin, X.-F., An, D. S., Chen, I. S. Y., Baltimore, D.
(2003). Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc. Natl. Acad. Sci. USA
100: 183-188
[Abstract]
[Full Text]
-
Scripture-Adams, D. D., Brooks, D. G., Korin, Y. D., Zack, J. A.
(2002). Interleukin-7 Induces Expression of Latent Human Immunodeficiency Virus Type 1 with Minimal Effects on T-Cell Phenotype. J. Virol.
76: 13077-13082
[Abstract]
[Full Text]
-
Korin, Y. D., Brooks, D. G., Brown, S., Korotzer, A., Zack, J. A.
(2002). Effects of Prostratin on T-Cell Activation and Human Immunodeficiency Virus Latency. J. Virol.
76: 8118-8123
[Abstract]
[Full Text]
-
Lundquist, C. A., Tobiume, M., Zhou, J., Unutmaz, D., Aiken, C.
(2002). Nef-Mediated Downregulation of CD4 Enhances Human Immunodeficiency Virus Type 1 Replication in Primary T Lymphocytes. J. Virol.
76: 4625-4633
[Abstract]
[Full Text]
-
Brooks, D. G., Zack, J. A.
(2002). Effect of Latent Human Immunodeficiency Virus Infection on Cell Surface Phenotype. J. Virol.
76: 1673-1681
[Abstract]
[Full Text]
-
Cole, S. W., Naliboff, B. D., Kemeny, M. E., Griswold, M. P., Fahey, J. L., Zack, J. A.
(2001). Impaired response to HAART in HIV-infected individuals with high autonomic nervous system activity. Proc. Natl. Acad. Sci. USA
98: 12695-12700
[Abstract]
[Full Text]
-
Poles, M. A., Elliott, J., Taing, P., Anton, P. A., Chen, I. S. Y.
(2001). A Preponderance of CCR5+ CXCR4+ Mononuclear Cells Enhances Gastrointestinal Mucosal Susceptibility to Human Immunodeficiency Virus Type 1 Infection. J. Virol.
75: 8390-8399
[Abstract]
[Full Text]
-
Logg, C. R., Logg, A., Tai, C.-K., Cannon, P. M., Kasahara, N.
(2001). Genomic Stability of Murine Leukemia Viruses Containing Insertions at the Env-3' Untranslated Region Boundary. J. Virol.
75: 6989-6998
[Abstract]
[Full Text]
-
Zhu, Y., Gelbard, H. A., Roshal, M., Pursell, S., Jamieson, B. D., Planelles, V.
(2001). Comparison of Cell Cycle Arrest, Transactivation, and Apoptosis Induced by the Simian Immunodeficiency Virus SIVagm and Human Immunodeficiency Virus Type 1 vpr Genes. J. Virol.
75: 3791-3801
[Abstract]
[Full Text]
-
Duus, K. M., Miller, E. D., Smith, J. A., Kovalev, G. I., Su, L.
(2001). Separation of Human Immunodeficiency Virus Type 1 Replication from nef-Mediated Pathogenesis in the Human Thymus. J. Virol.
75: 3916-3924
[Abstract]
[Full Text]
-
Steinberger, P., Andris-Widhopf, J., Buhler, B., Torbett, B. E., Barbas, C. F. III
(2000). Functional deletion of the CCR5 receptor by intracellular immunization produces cells that are refractory to CCR5-dependent HIV-1 infection and cell fusion. Proc. Natl. Acad. Sci. USA
97: 805-810
[Abstract]
[Full Text]
-
Koka, P. S., Jamieson, B. D., Brooks, D. G., Zack, J. A.
(1999). Human Immunodeficiency Virus Type 1-Induced Hematopoietic Inhibition Is Independent of Productive Infection of Progenitor Cells In Vivo. J. Virol.
73: 9089-9097
[Abstract]
[Full Text]
-
Verhasselt, B., Naessens, E., Verhofstede, C., De Smedt, M., Schollen, S., Kerre, T., Vanhecke, D., Plum, J.
(1999). Human Immunodeficiency Virus nef Gene Expression Affects Generation and Function of Human T Cells, But Not Dendritic Cells. Blood
94: 2809-2818
[Abstract]
[Full Text]
-
Chêne, L., Nugeyre, M.-T., Guillemard, E., Moulian, N., Barré-Sinoussi, F., Israël, N.
(1999). Thymocyte-Thymic Epithelial Cell Interaction Leads to High-Level Replication of Human Immunodeficiency Virus Exclusively in Mature CD4+ CD8- CD3+ Thymocytes: a Critical Role for Tumor Necrosis Factor and Interleukin-7. J. Virol.
73: 7533-7542
[Abstract]
[Full Text]
-
An, D. S., Morizono, K., Li, Q.-X., Mao, S. H., Lu, S., Chen, I. S. Y.
(1999). An Inducible Human Immunodeficiency Virus Type 1 (HIV-1) Vector Which Effectively Suppresses HIV-1 Replication. J. Virol.
73: 7671-7677
[Abstract]
[Full Text]
-
Amado, R. G., Jamieson, B. D., Cortado, R., Cole, S. W., Zack, J. A.
(1999). Reconstitution of Human Thymic Implants Is Limited by Human Immunodeficiency Virus Breakthrough during Antiretroviral Therapy. J. Virol.
73: 6361-6369
[Abstract]
[Full Text]
-
Korin, Y. D., Zack, J. A.
(1999). Nonproductive Human Immunodeficiency Virus Type 1 Infection in Nucleoside-Treated G0 Lymphocytes. J. Virol.
73: 6526-6532
[Abstract]
[Full Text]
-
Cole, S. W., Jamieson, B. D., Zack, J. A.
(1999). cAMP Up-Regulates Cell Surface Expression of Lymphocyte CXCR4: Implications for Chemotaxis and HIV-1 Infection. J. Immunol.
162: 1392-1400
[Abstract]
[Full Text]