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*AIDS
The Journal of Immunology, 2005, 174: 7524-7530.
Copyright © 2005 by The American Association of Immunologists

HIV-1 Viral Escape in Infancy Followed by Emergence of a Variant-Specific CTL Response1

Margaret E. Feeney2,*,{dagger}, Yanhua Tang*, Katja Pfafferott{ddagger}, Kathleen A. Roosevelt*, Rika Draenert*,§, Alicja Trocha*, Xu G. Yu*, Cori Verrill*,§, Todd Allen*, Corey Moore, Simon Mallal, Sandra Burchett{dagger}, Kenneth McIntosh{dagger}, Stephen I. Pelton||, M. Anne St. John#, Rohan Hazra**, Paul Klenerman{ddagger}, Marcus Altfeld*, Bruce D. Walker*,§ and Philip J. R. Goulder{ddagger}

* Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; {dagger} Children’s Hospital, Boston, MA 02115; {ddagger} Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom; § Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115; Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital, Perth, Australia; || Boston Medical Center, Boston, MA 02118;# Queen Elizabeth Hospital, Bridgetown, Barbados; and ** National Cancer Institute, HIV and AIDS Malignancy Branch, Bethesda, MD 20892

Mutational escape from the CTL response represents a major driving force for viral diversification in HIV-1-infected adults, but escape during infancy has not been described previously. We studied the immune response of perinatally infected children to an epitope (B57-TW10) that is targeted early during acute HIV-1 infection in adults expressing HLA-B57 and rapidly mutates under this selection pressure. Viral sequencing revealed the universal presence of escape mutations within TW10 among B57- and B5801-positive children. Mutations in TW10 and other B57-restricted epitopes arose early following perinatal infection of B57-positive children born to B57-negative mothers. Surprisingly, the majority of B57/5801-positive children exhibited a robust response to the TW10 escape variant while recognizing the wild-type epitope weakly or not at all. These data demonstrate that children, even during the first years of life, are able to mount functional immune responses of sufficient potency to drive immune escape. Moreover, our data suggest that the consequences of immune escape may differ during infancy because most children mount a strong variant-specific immune response following escape, which is rarely seen in adults. Taken together, these findings indicate that the developing immune system of children may exhibit greater plasticity in responding to a continually evolving chronic viral infection.




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