Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1 isolates of subtypes B and C.
Continual human immunodeficiency virus type 1 (HIV-1) evolution and expansion within the human population have led to unequal distribution of HIV-1 group M subtypes. In particular, recent outgrowth of subtype C in southern Africa, India, and China has fueled speculation that subtype C isolates may be more fit in vivo. In this study, nine subtype B and six subtype C HIV-1 isolates were added to peripheral blood mononuclear cell cultures for a complete pairwise competition experiment. All subtype C HIV-1 isolates were less fit than subtype B isolates (P < 0.0001), but intrasubtype variations in HIV-1 fitness were not significant. Increased fitness of subtype B over subtype C was also observed in primary CD4(+) T cells and macrophages from different human donors but not in skin-derived human Langerhans cells. Detailed analysis of the retroviral life cycle during several B and C virus competitions indicated that the efficiency of host cell entry may have a significant impact on relative fitness. Furthermore, phyletic analyses of fitness differences suggested that, for a recombined subtype B/C HIV-1 isolate, higher fitness mapped to the subtype B env gene rather than the subtype C gag and pol genes. These results suggest that subtype B and C HIV-1 may be transmitted with equal efficiency (Langerhans cell data) but that subtype C isolates may be less fit following initial infection (T-cell and macrophage data) and may lead to slower disease progression.
Ball
Sarah C
SC
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Abraha
Awet
A
Collins
Kalonji R
KR
Marozsan
Andre J
AJ
Baird
Heather
H
Quiñones-Mateu
Miguel E
ME
Penn-Nicholson
Adam
A
Murray
Michael
M
Richard
Nathalie
N
Lobritz
Michael
M
Zimmerman
Peter A
PA
Kawamura
Tatsuyoshi
T
Blauvelt
Andrew
A
Arts
Eric J
EJ
D002478:Cells, Cultured; D015752:Genes, env; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000502:physiology*; D013045:Species Specificity; D014779:Virus Replication
D019713:Receptors, CCR5