Genomic analysis of HIV type 1 strains derived from a mother and child pair of long-term nonprogressors.
To investigate the viral features of long-term nonprogressive HIV-1 infection and the selection of viral genomes, we studied serial complete HIV-1 sequences obtained from a mother-child pair, both long-term nonprogressors. Analysis of four genomic sequences demonstrated that all viral genes were intact, lacking major deletions or premature stop codons to easily explain the slow disease progression. These data suggest that viral attenuation, if present, was caused by subtle sequence variations or virus-host interactions. Serial sequences from an HIV-1-infected mother-child pair afforded us the opportunity to examine the immune selection of HIV-1 sequences years after transmission between individuals. We demonstrated that the daughter's strains were most likely subjected to immunoselection or immunoediting according to the presence of novel MHC class I alleles that differed between mother and daughter. An analysis of nef-specific cytotoxic T-lymphocyte responses in the child, whose HIV-1 nef sequence differed from the maternal nef, supported this interpretation. This study highlights the potential of full genome analysis in the investigation of pathogenesis and immune selection during HIV-1 evolution.
Reinis
Milan
M
Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.
Weiser
Barbara
B
Kuiken
Carla
C
Dong
Tao
T
Lang
Dorothy
D
Nachman
Sharon
S
Zhang
Yonghong
Y
Rowland-Jones
Sarah
S
Burger
Harold
H
D000328:Adult; D002675:Child, Preschool; D018450:Disease Progression; D019143:Evolution, Molecular; D005260:Female; D015693:Gene Products, nef / Q000737:chemistry; D005805:Genes, MHC Class I; D015658:HIV Infections / Q000235:genetics*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008969:Molecular Sequence Data; D011247:Pregnancy; D012191:Retroviridae Proteins / Q000737:chemistry; D012641:Selection, Genetic; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D012191:Retroviridae Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus