Access

Letters to Nature

Nature 420, 434-439 (28 November 2002) | doi:10.1038/nature01200; Received 5 July 2002; Accepted 13 September 2002

Open Innovation Challenges

naturejobs

More science jobs
Post a job for free

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus

Marcus Altfeld1,2, Todd M. Allen1,2, Xu G. Yu1, Mary N. Johnston1, Deepak Agrawal1, Bette T. Korber3, David C. Montefiori4, David H. O'Connor5, Ben T. Davis1, Paul K. Lee1, Erica L. Maier1, Jason Harlow1, Philip J. R. Goulder1,6, Christian Brander1, Eric S. Rosenberg1 & Bruce D. Walker1

  1. Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129, USA
  2. Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
  3. Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
  4. Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA
  5. Department of Pediatrics, Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford OX3 7LJ, UK
  6. These authors contributed equally to this work

Correspondence to: Bruce D. Walker1 Correspondence and requests for materials should be addressed to B.D.W. (e-mail: Email: bwalker@partners.org).

Top

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection1, 2, 3. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.

  1. Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129, USA
  2. Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
  3. Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
  4. Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA
  5. Department of Pediatrics, Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford OX3 7LJ, UK
  6. These authors contributed equally to this work

Correspondence to: Bruce D. Walker1 Correspondence and requests for materials should be addressed to B.D.W. (e-mail: Email: bwalker@partners.org).