This Article Full Text Full Text (PDF) 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 Pedroza-Martins, L. Articles by Uittenbogaart, C. H. Search for Related Content PubMed PubMed Citation Articles by Pedroza-Martins, L. Articles by Uittenbogaart, C. H.

 Previous Article  |  Next Article 

Journal of Virology, July 2002, p. 6929-6943, Vol. 76, No. 14
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.14.6929-6943.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Impact of Cytokines on Replication in the Thymus of Primary Human Immunodeficiency Virus Type 1 Isolates from Infants

Departments of Microbiology, Immunology, and Molecular Genetics,¹ Biostatistics, and,² Pediatrics, UCLA AIDS Institute,⁴ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California,⁵ Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium³

Received 1 November 2001/ Accepted 10 April 2002

Early infection of the thymus with the human immunodeficiency virus (HIV) may explain the more rapid disease progression among children infected in utero than in children infected intrapartum. Therefore, we analyzed infection of thymocytes in vitro by HIV type 1 primary isolates, obtained at or near birth, from 10 children with different disease outcomes. HIV isolates able to replicate in the thymus and impact thymopoiesis were present in all infants, regardless of the timing of viral transmission and the rate of disease progression. Isolates from newborns utilized CCR5, CXCR4, or both chemokine receptors to enter thymocytes. Viral expression was observed in discrete thymocyte subsets postinfection with HIV isolates using CXCR4 (X4) and isolates using CCR5 (R5), despite the wider distribution of CXCR4 in the thymus. In contrast to previous findings, the X4 primary isolates were not more cytopathic for thymocytes than were the R5 isolates. The cytokines interleukin-2 (IL-2), IL-4, and IL-7 increased HIV replication in the thymus by inducing differentiation and expansion of mature CD27⁺ thymocytes expressing CXCR4 or CCR5. IL-2 and IL-4 together increased expression of CXCR4 and CCR5 in this population, whereas IL-4 and IL-7 increased CXCR4 but not CCR5 expression. IL-2 plus IL-4 increased the viral production of all pediatric isolates, but IL-4 and IL-7 had a significantly higher impact on the replication of X4 isolates compared to R5 isolates. Our studies suggest that coreceptor use by HIV primary isolates is important but is not the sole determinant of HIV pathogenesis in the thymus.

This article has been cited by other articles:

• An, D. S., Poon, B., Fang, R. H. T., Weijer, K., Blom, B., Spits, H., Chen, I. S. Y., Uittenbogaart, C. H. (2007). Use of a Novel Chimeric Mouse Model with a Functionally Active Human Immune System To Study Human Immunodeficiency Virus Type 1 Infection. CVI 14: 391-396 [Abstract] [Full Text]  
• Gurney, K. B., Uittenbogaart, C. H. (2006). Human Immunodeficiency Virus Persistence and Production in T-Cell Development. CVI 13: 1237-1245 [Abstract] [Full Text]  
• Muthukumar, A., Zhou, D., Paiardini, M., Barry, A. P., Cole, K. S., McClure, H. M., Staprans, S. I., Silvestri, G., Sodora, D. L. (2005). Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys. Blood 106: 3839-3845 [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]  
• Gurney, K. B., Colantonio, A. D., Blom, B., Spits, H., Uittenbogaart, C. H. (2004). Endogenous IFN-{alpha} Production by Plasmacytoid Dendritic Cells Exerts an Antiviral Effect on Thymic HIV-1 Infection. J. Immunol. 173: 7269-7276 [Abstract] [Full Text]  
• Reyes, R. A., Canfield, D. R., Esser, U., Adamson, L. A., Brown, C. R., Cheng-Mayer, C., Gardner, M. B., Harouse, J. M., Luciw, P. A. (2004). Induction of Simian AIDS in Infant Rhesus Macaques Infected with CCR5- or CXCR4-Utilizing Simian-Human Immunodeficiency Viruses Is Associated with Distinct Lesions of the Thymus. J. Virol. 78: 2121-2130 [Abstract] [Full Text]  
• Muthukumar, A., Wozniakowski, A., Gauduin, M.-C., Paiardini, M., McClure, H. M., Johnson, R. P., Silvestri, G., Sodora, D. L. (2004). Elevated interleukin-7 levels not sufficient to maintain T-cell homeostasis during simian immunodeficiency virus-induced disease progression. Blood 103: 973-979 [Abstract] [Full Text]  
• Napolitano, L. A., Stoddart, C. A., Hanley, M. B., Wieder, E., McCune, J. M. (2003). Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice. J. Immunol. 171: 645-654 [Abstract] [Full Text]