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. 1989 May;63(5):2361–2365. doi: 10.1128/jvi.63.5.2361-2365.1989

Cell-to-cell transmission of human immunodeficiency virus type 1 in the presence of azidothymidine and neutralizing antibody.

P Gupta 1, R Balachandran 1, M Ho 1, A Enrico 1, C Rinaldo 1
PMCID: PMC250658  PMID: 2704079

Abstract

Very few peripheral blood lymphocytes of seropositive individuals are presumably actively infected with human immunodeficiency virus type 1 (HIV-1). During coculture of lymphocytes of a seropositive individual with mitogen-stimulated normal peripheral blood lymphocytes, the number of infected cells becomes amplified such that detectable HIV-1 is produced. We report here that in addition to transmission by extracellular virus, cell-to-cell transmission is responsible for spreading HIV-1 infection from infected to uninfected cells. Azidothymidine and virus-neutralizing antibody had no effect on cell-to-cell transmission of HIV-1. Monoclonal antibodies to the CD4 receptor, but not to the CD3 receptor, prevented cell-to-cell transmission, which suggests that CD4 receptor-mediated cell fusion is involved in cell-to-cell transmission. Spread of infection in a cell-to-cell manner may be important in development of drug therapies for HIV-1 infection.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BLACK F. L., MELNICK J. L. Microepidemiology of poliomyelitis and herpes-B infections: spread of the viruses within tissue cultures. J Immunol. 1955 Mar;74(3):236–242. [PubMed] [Google Scholar]
  2. Balachandran R., Thampatty P., Rinaldo C., Gupta P. Use of cryopreserved normal peripheral blood lymphocytes for isolation of human immunodeficiency virus from seropositive men. J Clin Microbiol. 1988 Mar;26(3):595–597. doi: 10.1128/jcm.26.3.595-597.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  4. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  5. Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
  6. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  7. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  8. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. doi: 10.1073/pnas.83.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Levy J. A., Hoffman A. D., Kramer S. M., Landis J. A., Shimabukuro J. M., Oshiro L. S. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science. 1984 Aug 24;225(4664):840–842. doi: 10.1126/science.6206563. [DOI] [PubMed] [Google Scholar]
  10. Levy J. A., Shimabukuro J. Recovery of AIDS-associated retroviruses from patients with AIDS or AIDS-related conditions and from clinically healthy individuals. J Infect Dis. 1985 Oct;152(4):734–738. doi: 10.1093/infdis/152.4.734. [DOI] [PubMed] [Google Scholar]
  11. Lifson J. D., Feinberg M. B., Reyes G. R., Rabin L., Banapour B., Chakrabarti S., Moss B., Wong-Staal F., Steimer K. S., Engleman E. G. Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature. 1986 Oct 23;323(6090):725–728. doi: 10.1038/323725a0. [DOI] [PubMed] [Google Scholar]
  12. Lodmell D. L., Ewalt L. C. Immune sera and antiglycoprotein monoclonal antibodies inhibit in vitro cell-to-cell spread of pathogenic rabies viruses. J Virol. 1987 Oct;61(10):3314–3318. doi: 10.1128/jvi.61.10.3314-3318.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McDougal J. S., Mawle A., Cort S. P., Nicholson J. K., Cross G. D., Scheppler-Campbell J. A., Hicks D., Sligh J. Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. J Immunol. 1985 Nov;135(5):3151–3162. [PubMed] [Google Scholar]
  14. Mitsuya H., Weinhold K. J., Furman P. A., St Clair M. H., Lehrman S. N., Gallo R. C., Bolognesi D., Barry D. W., Broder S. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096–7100. doi: 10.1073/pnas.82.20.7096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Prince A. M., Pascual D., Bardina-Kosolopov L., Kurokawa D., Baker L., Rubinstein P. Neutralizing antibody to the AIDS virus. Prevalence, clinical significance and virus strain specificity. Antibiot Chemother (1971) 1987;38:151–158. doi: 10.1159/000414229. [DOI] [PubMed] [Google Scholar]
  16. Robert-Guroff M., Brown M., Gallo R. C. HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex. Nature. 1985 Jul 4;316(6023):72–74. doi: 10.1038/316072a0. [DOI] [PubMed] [Google Scholar]
  17. WELLER T. H. Serial propagation in vitro of agents producing inclusion bodies derived from varicella and herpes zoster. Proc Soc Exp Biol Med. 1953 Jun;83(2):340–346. doi: 10.3181/00379727-83-20354. [DOI] [PubMed] [Google Scholar]
  18. Yarchoan R., Broder S. Development of antiretroviral therapy for the acquired immunodeficiency syndrome and related disorders. A progress report. N Engl J Med. 1987 Feb 26;316(9):557–564. doi: 10.1056/NEJM198702263160925. [DOI] [PubMed] [Google Scholar]

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