Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus.
The predictability of virus-host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape.
Draenert
Rika
R
Howard Hughes Medical Institute, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Allen
Todd M
TM
Liu
Yang
Y
Wrin
Terri
T
Chappey
Colombe
C
Verrill
Cori L
CL
Sirera
Guillem
G
Eldridge
Robert L
RL
Lahaie
Matthew P
MP
Ruiz
Lidia
L
Clotet
Bonaventura
B
Petropoulos
Christos J
CJ
Walker
Bruce D
BD
Martinez-Picado
Javier
J
D000328:Adult; D019943:Amino Acid Substitution; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D018791:CD4 Lymphocyte Count / Q000379:methods; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D019143:Evolution, Molecular; D005260:Female; D005500:Follow-Up Studies; D015686:Gene Products, env / Q000235:genetics* / Q000276:immunology; D006679:HIV Seropositivity / Q000097:blood / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D008297:Male; D017354:Point Mutation
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env