HIV-1 superinfection despite broad cd8+ T-cell responses containing replication of the primary virus

Marcus Altfeld, Todd M. Allen, Xu G. Yu, Mary N. Johnston, Deepak Agrawal, Bette T. Korber, David C. Montefiori, David H. O'Connor, Ben T. Davis, Paul K. Lee, Erica L. Maier, Jason Harlow, Philip J.R. Goulder, Christian Brander, Eric S. Rosenberg, Bruce D. Walker

Research output: Contribution to journalArticle

274 Citations (Scopus)

Abstract

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection1-3. 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.

Original languageEnglish (US)
Pages (from-to)434-439
Number of pages6
JournalNature
Volume420
Issue number6914
DOIs
StatePublished - Nov 28 2002
Externally publishedYes

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Superinfection
Virus Replication
HIV-1
T-Lymphocytes
Viremia
Viruses
Immunity
Cercopithecine Herpesvirus 1
gag Gene Products
Integrases
T-Lymphocyte Epitopes
Plasma Cells
HIV Infections
Epitopes
Vaccines
Public Health

ASJC Scopus subject areas

  • General

Cite this

Altfeld, M., Allen, T. M., Yu, X. G., Johnston, M. N., Agrawal, D., Korber, B. T., ... Walker, B. D. (2002). HIV-1 superinfection despite broad cd8+ T-cell responses containing replication of the primary virus. Nature, 420(6914), 434-439. https://doi.org/10.1038/nature01200

HIV-1 superinfection despite broad cd8+ T-cell responses containing replication of the primary virus. / Altfeld, Marcus; Allen, Todd M.; Yu, Xu G.; Johnston, Mary N.; Agrawal, Deepak; Korber, Bette T.; Montefiori, David C.; O'Connor, David H.; Davis, Ben T.; Lee, Paul K.; Maier, Erica L.; Harlow, Jason; Goulder, Philip J.R.; Brander, Christian; Rosenberg, Eric S.; Walker, Bruce D.

In: Nature, Vol. 420, No. 6914, 28.11.2002, p. 434-439.

Research output: Contribution to journalArticle

Altfeld, M, Allen, TM, Yu, XG, Johnston, MN, Agrawal, D, Korber, BT, Montefiori, DC, O'Connor, DH, Davis, BT, Lee, PK, Maier, EL, Harlow, J, Goulder, PJR, Brander, C, Rosenberg, ES & Walker, BD 2002, 'HIV-1 superinfection despite broad cd8+ T-cell responses containing replication of the primary virus', Nature, vol. 420, no. 6914, pp. 434-439. https://doi.org/10.1038/nature01200
Altfeld M, Allen TM, Yu XG, Johnston MN, Agrawal D, Korber BT et al. HIV-1 superinfection despite broad cd8+ T-cell responses containing replication of the primary virus. Nature. 2002 Nov 28;420(6914):434-439. https://doi.org/10.1038/nature01200
Altfeld, Marcus ; Allen, Todd M. ; Yu, Xu G. ; Johnston, Mary N. ; Agrawal, Deepak ; Korber, Bette T. ; Montefiori, David C. ; O'Connor, David H. ; Davis, Ben T. ; Lee, Paul K. ; Maier, Erica L. ; Harlow, Jason ; Goulder, Philip J.R. ; Brander, Christian ; Rosenberg, Eric S. ; Walker, Bruce D. / HIV-1 superinfection despite broad cd8+ T-cell responses containing replication of the primary virus. In: Nature. 2002 ; Vol. 420, No. 6914. pp. 434-439.
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