Study of the dynamics of neutralization escape mutants in a chimpanzee naturally infected with the simian immunodeficiency virus SIVcpz-ant

Abstract

Here we report on the use of spectral map analysis of time-paired sequential neutralization data of 11 serum samples of a chimpanzee naturally infected with a simian immunodeficiency virus (SIVcpz-ant) and 8 primary consecutive SIVcpz-ant isolates, taken at about 4-month intervals. The analysis reveals the existence of three SIVcpz-ant isolate and serum neutralization clusters. Each cluster groups virus isolates and/or sera based on similarities of their neutralization spectra. On average, neutralization escape mutants emerged after 15 months and mounted a neutralization response approximately 8 months later. The entire gp160 regions of eight consecutive isolates were sequenced and analyzed by a new statistical method called polygram, which allowed the deduction of amino acid sequence motifs of gp160 which were specific for SIVcpz-ant isolates belonging to the same isolate neutralization clusters. Changes in specific amino acid quadruplets in V1, V2, C3, V4, V5, and CD4 domains of gp120 and gp40 were seen to correlate with the neutralization clusters with most of the specific changes occuring in the V4 region. This method of analysis may facilitate an understanding of the study of the dynamic interplay between human immunodeficiency virus (HIV) and host neutralization responses as well as providing possible insights into mechanisms of persistence of HIV-1-related lentiviruses in their natural hosts.

Identification and characterization of sera from HIV-infected individuals with broad cross-neutralizing activity against group M (env clade A-H) and group O primary HIV-1 isolates

“…Although the production of antibodies is efficient and used as a marker for serological diagnosis of infection, most antibodies do not exert neutralizing activity against primary virus isolates. Antibodies with neutralizing capacity against primary isolates emerge relatively late after seroconversion (>1 year post-infection) when the neutralizing activity is monitored on primary lymphocytes, and their neutralization spectrum broadens in time, revealing a temporal evolution of the humoral immune response generating cross-reactive neutralizing antibodies [Moog et al, 1997;Nyambi et al, 1997]. A correlation between the appearance of neutralizing antibodies and a decrease in viral load has been observed [Lathey et al, 1997].…”

In vitro susceptibility to infection with SIVcpz and HIV‐1 is lower in chimpanzee than in human peripheral blood mononuclear cells*

“…Immunologic and virologic evidence on HIV-1-and SIVcpz-infected chimpanzees suggests that viral factors are unlikely to be the cause for their long-term AIDS-free infection. There is no consistent evidence that vigorous specific humoral or cellular immune responses are responsible for delayed disease progression in infected chimpanzees Nyambi et al, 1997;Kestens et al, 1998;Ondoa et al, 2001]. In HIV-1-infected humans and the SIVmacinfected macaque model, it has been established that the post-acute viral replication set point has an important prognostic significance [Mellors et al, 1995[Mellors et al, , 1996ten Haaft et al, 1998].…”

Longitudinal comparison of virus load parameters and CD8 T‐cell suppressive capacity in two SIVcpz‐infected chimpanzees

“…Of the simian immunodeficiency virus (SIV)cpz-infected chimpanzees identified to date, none has had any evidence of AIDS-related disease [39,47]. Similarly, of the more than 100 chimpanzees infected with HIV-1, only one has developed hematological changes compatible with AIDS [22,23,38,46,62].…”