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Journal of Virology, May 1999, p. 3975-3985, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Frequent Detection of Escape from Cytotoxic T-Lymphocyte Recognition in Perinatal Human Immunodeficiency Virus (HIV) Type 1 Transmission: the Ariel Project for the Prevention of Transmission of HIV from Mother to Infant

Cara C. Wilson,1,dagger R. Clark Brown,2 Bette T. Korber,3 Barbara M. Wilkes,1 Debbie J. Ruhl,1 Doreen Sakamoto,2 Kevin Kunstman,2 Katherine Luzuriaga,4 I. Celine Hanson,5 Susan M. Widmayer,6 Andrew Wiznia,7 Sheila Clapp,8 Arthur J. Ammann,9 Richard A. Koup,1,Dagger Steven M. Wolinsky,2,* Bruce D. Walker,1,* and The Ariel Project Investigators§

AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 021141; Northwestern University School of Medicine, Chicago, Illinois 606112; Santa Fe Institute, Santa Fe, New Mexico 87501, and Los Alamos National Laboratory, Los Alamos, New Mexico 875453; University of Massachusetts Medical School, Worcester, Massachusetts 016054; Department of Pediatrics, Baylor College of Medicine, Houston, Texas 770305; Children's Diagnostic & Treatment Center, Fort Lauderdale, Florida 333016; Bronx-Lebanon Hospital Center, Bronx, New York 104577; Department of Pediatrics, University of California San Francisco Medical Center, San Francisco, California 941438; and Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 100169

Received 11 September 1998/Accepted 27 January 1999

Host immunologic factors, including human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL), are thought to contribute to the control of HIV type 1 (HIV-1) replication and thus delay disease progression in infected individuals. Host immunologic factors are also likely to influence perinatal transmission of HIV-1 from infected mother to infant. In this study, the potential role of CTL in modulating HIV-1 transmission from mother to infant was examined in 11 HIV-1-infected mothers, 3 of whom transmitted virus to their offspring. Frequencies of HIV-1-specific human leukocyte antigen class I-restricted CTL responses and viral epitope amino acid sequence variation were determined in the mothers and their infected infants. Maternal HIV-1-specific CTL clones were derived from each of the HIV-1-infected pregnant women. Amino acid substitutions within the targeted CTL epitopes were more frequently identified in transmitting mothers than in nontransmitting mothers, and immune escape from CTL recognition was detected in all three transmitting mothers but in only one of eight nontransmitting mothers. The majority of viral sequences obtained from the HIV-1-infected infant blood samples were susceptible to maternal CTL. These findings demonstrate that epitope amino acid sequence variation and escape from CTL recognition occur more frequently in mothers that transmit HIV-1 to their infants than in those who do not. However, the transmitted virus can be a CTL susceptible form, suggesting inadequate in vivo immune control.

* Corresponding author. Mailing address for Steven M. Wolinsky: Northwestern University School of Medicine, 303 E. Chicago Ave., Chicago, IL 60611. Phone: (312) 908-5210. Fax: (312) 908-4588. E-mail: s-wolinsky{at}nwu.edu. Mailing address for Bruce D. Walker: AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Fruit Street, Boston, Massachusetts 02114. Phone: (617) 724-8332. Fax: (617) 726-4691. E-mail: bwalker{at}helix.mgh.harvard.edu.

dagger Present address: Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262.

Dagger Present address: University of Texas Southwestern Medical School, Dallas, Tex.

§ The Ariel Project is a Pediatric AIDS Foundation-sponsored project. Clinical site principal investigators include S.M.W., I.C.H., A.W., and K.L., as well as Russell B. Van Dyke (Tulane University of Medicine, New Orleans, La.), Arlene Bardeguez (UMD-New Jersey Medical School, Newark, N.J.), and Richard R. Viscarello (Maternal Fetal Care, P.C., Stamford, Conn.). Core investigators include B.T.K., B.D.W., and S.M.W., as well as David Ho and Rick Koup (Aaron Diamond AIDS Research Center, New York, N.Y.), Irvin Chen and Paul Krogstad, (University of California, Los Angeles), and James Mullins (University of Washington, Seattle). A.J.A. and S.C. are study coordinators. The Data Management Center is coordinated by B.T.K., David McDonald, and Robert Funkhouser.

Journal of Virology, May 1999, p. 3975-3985, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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