Viral evolution in macaques coinfected with CCR5- and CXCR4-tropic SHIVs in the presence or absence of vaccine-elicited anti-CCR5 SHIV neutralizing antibodies.
Macaques were immunized with SF162 Env-based gp140 immunogens and challenged simultaneously with the CCR5-tropic homologous SHIV(SF162P4) and the CXCR4-tropic heterologous SHIV(SF33A) viruses. Both mock-immunized and immunized animals became dually infected. Prior immunization preferentially reduced the viral replication of the homologous virus during primary infection but the relative replication of the two coinfecting viruses during chronic infection was unaffected by prior immunization, despite the fact that five of six immunized animals maintained a significantly lower overall viral replication that the control animals. Neutralizing antibodies participated in controlling the replication of SHIV(SF162P4), but not that of SHIV(SF33A). Dual infection resulted in the emergence and predominance within the circulating CCR5 virus pool, of a variant with a distinct neutralization phenotype. The signature of this variant was the presence of three amino acid changes in gp120, two of which were located in the receptor and coreceptor binding sites. Also, a significant fraction of the viruses circulating in the blood, as early as two weeks post-infection, was recombinants and prior immunization did not prevent their emergence. These findings provide new insights into the dynamic interaction of CCR5- and CXCR4-tropic HIV isolates that are potentially relevant in better understanding HIV-mediated pathogenesis.
Burke
Brian
B
Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
Derby
Nina R
NR
Kraft
Zane
Z
Saunders
Cheryl J
CJ
Dai
Chuanbin
C
Llewellyn
Nicholas
N
Zharkikh
Irina
I
Vojtech
Lucia
L
Zhu
Tuofu
T
Srivastava
Indresh K
IK
Barnett
Susan W
SW
Stamatatos
Leonidas
L
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000220:Adaptation, Biological; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000276:immunology / Q000502:physiology; D011995:Recombination, Genetic; D012641:Selection, Genetic; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D019562:Viral Load
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral; D019713:Receptors, CCR5