This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Naif, H. M.
Right arrow Articles by Cunningham, A. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Naif, H. M.
Right arrow Articles by Cunningham, A. L.
Right arrowPubmed/NCBI databases
*Protein*UniSTS

 Previous Article  |  Next Article 

Journal of Virology, June 1999, p. 4866-4881, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Definition of the Stage of Host Cell Genetic Restriction of Replication of Human Immunodeficiency Virus Type 1 in Monocytes and Monocyte-Derived Macrophages by Using Twins

Hassan M. Naif,1,* Shan Li,1 Mohammed Alali,1 Joon Chang,1 Carol Mayne,2 John Sullivan,3 and Anthony L. Cunningham1

Centre for Virus Research, Westmead Institutes of Health Research, Australian National Centre for HIV Virology Research, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145,1 Queensland Institute of Medical Research, Brisbane 4029,2 and Red Cross Blood Bank, Sydney 2001,3 Australia

Received 9 November 1998/Accepted 22 February 1999

Using identical (ID) twins, we have previously demonstrated that host cell genes exert a significant impact on productive human immunodeficiency virus (HIV) infection of monocytes and macrophages (J. Chang et al., J. Virol. 70:7792-7803, 1996). Therefore, the stage in the replication cycle at which these host genetic influences act was investigated in a study using 8 pairs of ID twins and 10 pairs of sex- and age-matched unrelated donors (URDs). In the first phase of the study, blood monocytes and monocyte-derived macrophages (MDM) of ID twins and URDs were infected with 15 HIV type 1 strains. Four well-characterized primary isolates and HIV-BaL were then examined in more detail. The host cell genetic effect in MDM was exerted predominantly prior to complete reverse transcription, as the HIV DNA level and p24 antigen levels were concordant (r = 0.91, P = 0.0001) and similar between the pairs of ID twin pairs (r = 0.96, P = 0.0001) but discordant between URD pairs (r = 0.11, P = 0.3) in both phases of the study. To further examine genetic influence on viral entry, we examined the proportion of CCR5 membrane expression on MDM. As expected, there was wide variability in proportion of MDM expressing CCR5 among URDs (r = 0.58, P = 0.2); however, this variability was significantly reduced between ID twin pairs (r = 0.81, P = 0.01). Differences in viral entry did not necessarily correlate with CCR5 expression, and only very low levels of CCR5 expression restricted HIV entry and production. In summary, the host cell genetic effect on HIV replication in macrophages appears to be exerted predominantly pre-reverse transcription. Although CCR5 was necessary for infection, other unidentified host genes are likely to limit productive infection.

* Corresponding author. Mailing address: Molecular Pathogenesis Laboratory, Centre for Virus Research, WIHR, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. Phone: 61-2-9845 6311. Fax: 61-2-9845 8300. E-mail: hassann{at}westmed.wh.usyd.edu.au.

Journal of Virology, June 1999, p. 4866-4881, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Llewellyn, N., Zioni, R., Zhu, H., Andrus, T., Xu, Y., Corey, L., Zhu, T. (2006). Continued evolution of HIV-1 circulating in blood monocytes with antiretroviral therapy: genetic analysis of HIV-1 in monocytes and CD4+ T cells of patients with discontinued therapy.. J. Leukoc. Biol. 80: 1118-1126 [Abstract] [Full Text]  
  • Bissel, S. J., Wang, G., Trichel, A. M., Murphey-Corb, M., Wiley, C. A. (2006). Longitudinal Analysis of Monocyte/Macrophage Infection in Simian Immunodeficiency Virus-Infected, CD8+ T-Cell-Depleted Macaques that Develop Lentiviral Encephalitis. Am. J. Pathol. 168: 1553-1569 [Abstract] [Full Text]  
  • Bleiber, G., May, M., Martinez, R., Meylan, P., Ott, J., Beckmann, J. S., Telenti, A., the Swiss HIV Cohort Study, (2005). Use of a Combined Ex Vivo/In Vivo Population Approach for Screening of Human Genes Involved in the Human Immunodeficiency Virus Type 1 Life Cycle for Variants Influencing Disease Progression. J. Virol. 79: 12674-12680 [Abstract] [Full Text]  
  • Ciuffi, A., Bleiber, G., Munoz, M., Martinez, R., Loeuillet, C., Rehr, M., Fischer, M., Gunthard, H. F., Oxenius, A., Meylan, P., Bonhoeffer, S., Trono, D., Telenti, A. (2004). Entry and Transcription as Key Determinants of Differences in CD4 T-Cell Permissiveness to Human Immunodeficiency Virus Type 1 Infection. J. Virol. 78: 10747-10754 [Abstract] [Full Text]  
  • Perez-Bercoff, D., David, A., Sudry, H., Barre-Sinoussi, F., Pancino, G. (2003). Fc{gamma} Receptor-Mediated Suppression of Human Immunodeficiency Virus Type 1 Replication in Primary Human Macrophages. J. Virol. 77: 4081-4094 [Abstract] [Full Text]  
  • Naif, H. M., Cunningham, A. L., Alali, M., Li, S., Nasr, N., Buhler, M. M., Schols, D., de Clercq, E., Stewart, G. (2002). A Human Immunodeficiency Virus Type 1 Isolate from an Infected Person Homozygous for CCR5{Delta}32 Exhibits Dual Tropism by Infecting Macrophages and MT2 Cells via CXCR4. J. Virol. 76: 3114-3124 [Abstract] [Full Text]  
  • Zhu, T., Muthui, D., Holte, S., Nickle, D., Feng, F., Brodie, S., Hwangbo, Y., Mullins, J. I., Corey, L. (2002). Evidence for Human Immunodeficiency Virus Type 1 Replication In Vivo in CD14+ Monocytes and Its Potential Role as a Source of Virus in Patients on Highly Active Antiretroviral Therapy. J. Virol. 76: 707-716 [Abstract] [Full Text]  
  • Gorry, P. R., Bristol, G., Zack, J. A., Ritola, K., Swanstrom, R., Birch, C. J., Bell, J. E., Bannert, N., Crawford, K., Wang, H., Schols, D., De Clercq, E., Kunstman, K., Wolinsky, S. M., Gabuzda, D. (2001). Macrophage Tropism of Human Immunodeficiency Virus Type 1 Isolates from Brain and Lymphoid Tissues Predicts Neurotropism Independent of Coreceptor Specificity. J. Virol. 75: 10073-10089 [Abstract] [Full Text]  
  • Mouland, A. J., Xu, H., Cui, H., Krueger, W., Munro, T. P., Prasol, M., Mercier, J., Rekosh, D., Smith, R., Barbarese, E., Cohen, E. A., Carson, J. H. (2001). RNA Trafficking Signals in Human Immunodeficiency Virus Type 1. Mol. Cell. Biol. 21: 2133-2143 [Abstract] [Full Text]  
  • Cunningham, A. L., Li, S, Juarez, J, Lynch, G, Alali, M., Naif, H. (2000). The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes. J. Leukoc. Biol. 68: 311-317 [Abstract] [Full Text]  
  • Zhu, T. (2000). HIV-1 genotypes in peripheral blood monocytes. J. Leukoc. Biol. 68: 338-344 [Abstract] [Full Text]  
  • Li, S., Juarez, J., Alali, M., Dwyer, D., Collman, R., Cunningham, A., Naif, H. M. (1999). Persistent CCR5 Utilization and Enhanced Macrophage Tropism by Primary Blood Human Immunodeficiency Virus Type 1 Isolates from Advanced Stages of Disease and Comparison to Tissue-Derived Isolates. J. Virol. 73: 9741-9755 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»