title: Comparison of HIV-1 nef and gag Variations and Host HLA Characteristics as Determinants of Disease Progression among HIV-1 Vertically Infected Kenyan Children.
abstract: OBJECTIVE
  Disease progression varies among HIV-1-infected individuals. The present study aimed to explore possible viral and host factors affecting disease progression in HIV-1-infected children.
  
  
  METHODS
  Since 2000, 102 HIV-1 vertically-infected children have been followed-up in Kenya. Here we studied 29 children (15 male/14 female) who started antiretroviral treatment at <5 years of age (rapid progressors; RP), and 32 (17 male/15 female) who started at >10 years of age (slow progressors; SP). Sequence variations in the HIV-1 gag and nef genes and the HLA class I-related epitopes were compared between the two groups.
  
  
  RESULTS
  Based on nef sequences, HIV-1 subtypes A1/D were detected in 62.5%/12.5% of RP and 66.7%/20% of SP, with no significant difference in subtype distribution between groups (p = 0.8). In the ten Nef functional domains, only the PxxP3 region showed significantly greater variation in RP (33.3%) than SP (7.7%, p = 0.048). Gag sequences did not significantly differ between groups. The reportedly protective HLA-A alleles, A*74:01, A*32:01 and A*26, were more commonly observed in SP (50.0%) than RP (11.1%, p = 0.010), whereas the reportedly disease-susceptible HLA-B*45:01 was more common in RP (33.3%) than SP (7.4%, p = 0.045). Compared to RP, SP showed a significantly higher median number of predicted HLA-B-related 12-mer epitopes in Nef (3 vs. 2, p = 0.037), HLA-B-related 11-mer epitopes in Gag (2 vs. 1, p = 0.029), and HLA-A-related 9-mer epitopes in Gag (4 vs. 1, p = 0.051). SP also had fewer HLA-C-related epitopes in Nef (median 4 vs. 5, p = 0.046) and HLA-C-related 11-mer epitopes in Gag (median 1 vs. 1.5, p = 0.044) than RP.
  
  
  CONCLUSIONS
  Compared to rapid progressors, slow progressors had more protective HLA-A alleles and more HLA-B-related epitopes in both the Nef and Gag proteins. These results suggest that the host factor HLA plays a stronger role in disease progression than the Nef and Gag sequence variations in HIV-1-infected Kenyan children.
authors: Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
authors: Matilda Chelimo
authors: MC
authors: Saina
authors: Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
authors: Xiuqiong
authors: X
authors: Bi
authors: Center for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors: Raphael
authors: R
authors: Lihana
authors: Center for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors: Raphael
authors: R
authors: Lwembe
authors: Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
authors: Azumi
authors: A
authors: Ishizaki
authors: Nyumbani Children's home, Nairobi, Kenya.
authors: Annie
authors: A
authors: Panikulam
authors: Nyumbani Children's home, Nairobi, Kenya.
authors: Tresa
authors: T
authors: Palakudy
authors: Department of pediatrics, University of Nairobi, Nairobi, Kenya.
authors: Rachel
authors: R
authors: Musoke
authors: Nyumbani Children's home, Nairobi, Kenya.
authors: Mary
authors: M
authors: Owens
authors: Center for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors: Elijah Maritim
authors: EM
authors: Songok
authors: Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
authors: Hiroshi
authors: H
authors: Ichimura
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000276:immunology / Q000635:transmission; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D007630:Kenya; D008297:Male; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus