Genetic characteristics of HIV-1 subtype C envelopes inducing cross-neutralizing antibodies.
This study aimed to characterize genetic features of HIV-1 subtype C envelope glycoproteins capable of eliciting cross-reactive neutralizing antibodies during natural infections. The gp160 sequences were determined for 36 HIV-1 subtype C isolates (donor viruses) from infected individuals residing in Malawi, Zimbabwe, Zambia and South Africa, whose sera displayed a range of cross-neutralizing activities against a panel of 5 subtype C and 5 subtype B viruses (panel viruses). Hierarchical clustering analysis of neutralization data of the panel viruses predicted phylogenetic relationships between subtype B and C panel viruses, suggesting some subtype-specific neutralization determinants. A similar comparison of subtype C donor viruses showed no significant correlation; however of three donor sequence pairs resolvable by phylogenetic analysis, two were also associated within the neutralization clustering dendrogram, suggesting that closely related viruses may elicit antibodies targeting common neutralization determinants. Significantly, viruses that had shorter V1-V4 loops induced antibodies that showed more neutralization breadth against the subtype C panel viruses (p=0.0135). This study indicates that that some structural features of envelope, such as shorter variable loops, may facilitate the elicitation of cross-reactive neutralizing antibodies in natural infections. Collectively these data provide some insights into design features of an envelope immunogen aimed at inducing neutralizing antibodies.
Rademeyer
Cecilia
C
Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town, Observatory 7925, Cape Town, South Africa.
Moore
Penny L
PL
Taylor
Natasha
N
Martin
Darren P
DP
Choge
Isaac A
IA
Gray
Elin S
ES
Sheppard
Haynes W
HW
Gray
Clive
C
Morris
Lynn
L
Williamson
Carolyn
C
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D016000:Cluster Analysis; D003429:Cross Reactions; D005260:Female; D019302:HIV Envelope Protein gp160 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008295:Malawi; D008297:Male; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D013019:South Africa; D015024:Zambia; D015030:Zimbabwe
D000914:Antibodies, Viral; D019302:HIV Envelope Protein gp160; D012367:RNA, Viral; C514797:gp160 protein, Human immunodeficiency virus 1