HIV-1 viral escape in infancy followed by emergence of a variant-specific CTL response.
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.
Feeney
Margaret E
ME
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. mfeeney@partners.org
Tang
Yanhua
Y
Pfafferott
Katja
K
Roosevelt
Kathleen A
KA
Draenert
Rika
R
Trocha
Alicja
A
Yu
Xu G
XG
Verrill
Cori
C
Allen
Todd
T
Moore
Corey
C
Mallal
Simon
S
Burchett
Sandra
S
McIntosh
Kenneth
K
Pelton
Stephen I
SI
St John
M Anne
MA
Hazra
Rohan
R
Klenerman
Paul
P
Altfeld
Marcus
M
Walker
Bruce D
BD
Goulder
Philip J R
PJ
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D014779:Virus Replication / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; C103707:HLA-B57 antigen