Biological and genetic evolution of HIV type 1 in two siblings with different patterns of disease progression.
To investigate the immunological and virological factors that may lead to different patterns of disease progression characteristic of HIV-1-infected children, two HIV-1-infected siblings, a slow and a fast progressor, were followed prospectively before the onset of highly active antiretroviral therapy. Viral coreceptor usage, including the use of CCR5/CXCR4 chimeric receptors, macrophage tropism, and sensitivity to the CC-chemokine RANTES, has been studied. An autologous and heterologous neutralizing antibody response has been documented using peripheral blood mononuclear cells- and GHOST(3) cell line-based assays. Viral evolution was investigated by env C2-V3 region sequence analysis. Although both siblings were infected with HIV-1 of the R5 phenotype, their viruses showed important biological differences. In the fast progressor there was a higher RANTES sensitivity of the early virus, an increased trend to change the mode of CCR5 receptor use, and a larger genetic evolution. Both children developed an autologous neutralizing antibody response starting from the second year with evidence of the continuous emergence of resistant variants. A marked viral genetic and phenotypic evolution was documented in the fast progressor sibling, which is accompanied by a high viral RANTES sensitivity and persistent neutralizing antibodies.
Ripamonti
Chiara
C
Viral Evolution and Transmission Unit, DIBIT, Fondazione Centro San Raffaele, Milan, Italy.
Leitner
Thomas
T
Laurén
Anna
A
Karlsson
Ingrid
I
Pastore
Angela
A
Cavarelli
Mariangela
M
Antonsson
Liselotte
L
Plebani
Anna
A
Fenyö
Eva Maria
EM
Scarlatti
Gabriella
G
D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018946:Chemokine CCL5 / Q000378:metabolism*; D002648:Child; D018450:Disease Progression; D019143:Evolution, Molecular; D005838:Genotype; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010641:Phenotype; D019707:Receptors, Chemokine / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism*; D035781:Siblings; D019562:Viral Load
D018946:Chemokine CCL5; D015483:HIV Antibodies; D019707:Receptors, Chemokine; D015728:Receptors, HIV