Replicative capacity of human immunodeficiency virus type 1 transmitted from mother to child is associated with pediatric disease progression rate.
Human immunodeficiency virus (HIV)-infected infants in the developing world typically progress to AIDS or death within the first 2 years of life. However, a minority progress relatively slowly. This study addresses the potential contribution of viral factors to HIV disease progression in eight infants selected from a well-characterized cohort of C clade HIV-infected infants, monitored prospectively from birth in Durban, South Africa. Three infants were defined as "progressors," and five were defined as "slow progressors." We observed that slow-progressor infants carry HIV isolates with significantly lower replicative capacity compared to virus from progressors. Furthermore, our data suggest a link between the attenuated viral phenotype and HLA-B* 57/5801 epitope-specific Gag mutational patterns of the transmitted virus and not to coreceptor usage or to the presence of Nef deletions or insertions. These data underline the importance of virus-host interactions and highlight the contribution of viral attenuation through Gag-specific CD8(+) T-cell escape mutations, among other factors, in the control of pediatric HIV infection.
Prado
Julia G
JG
Department of Pediatrics, University of Oxford, Oxford OX1 3SY, UK. jgarciaprado@irsicaixa.es
Prendergast
Andrew
A
Thobakgale
Christina
C
Molina
Claudia
C
Tudor-Williams
Gareth
G
Ndung'u
Thumbi
T
Walker
Bruce D
BD
Goulder
Philip
P
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D015683:Gene Products, gag / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015235:HLA-B Antigens / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion / Q000235:genetics*; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007700:Kinetics; D009154:Mutation; D013019:South Africa; D014779:Virus Replication
D015683:Gene Products, gag; D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; C103707:HLA-B57 antigen