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Frederic Bibollet-Ruche

Publications and source records attributed to Frederic Bibollet-Ruche.

At least 19 recordsLinked to original sources
PubMed2025

Plasmodium falciparum CyRPA Glycan Binding Does Not Explain Adaptation to Humans.

The human malaria parasite Plasmodium falciparum evolved from a parasite that infects gorillas, termed Plasmodium praefalciparum. The sialic acids on glycans on the surface of erythrocytes differ between humans and other apes. It has recently been shown that the P. falciparum cysteine-rich protective antigen (PfCyRPA) binds human sialoglycans as an essential step in the erythrocyte invasion pathway, while that of the chimpanzee parasite, Plasmodium reichenowi has affinities matching ape glycans. Two amino acid changes, at sites 154 and 209, were shown to be sufficient to switch glycan binding preferences and inferred to reflect adaptation of P. falciparum to humans. However, we show that sites 154 and 209 are identical in P. falciparum and P. praefalciparum, with no other differences located in or near the CyRPA glycan binding sites. Thus, the gorilla precursor appears to have already been preadapted to bind human sialoglycans.

Plasmodium falciparum↗
PubMed2006

Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins.

"Centralized" (ancestral and consensus) HIV-1 envelope immunogens induce broadly cross-reactive T cell responses in laboratory animals; however, their potential to elicit cross-reactive neutralizing antibodies has not been fully explored. Here, we report the construction of a panel of consensus subtype B (ConB) envelopes and compare their biologic, antigenic, and immunogenic properties to those of two wild-type Env controls from individuals with early and acute HIV-1 infection. Glycoprotein expressed from full-length (gp160), uncleaved (gp160-UNC), truncated (gp145), and N-linked glycosylation site deleted (gp160-201N/S) versions of the ConB env gene were packaged into virions and, except for the fusion defective gp160-UNC, mediated infection via the CCR5 co-receptor. Pseudovirions containing ConB Envs were sensitive to neutralization by patient plasma and monoclonal antibodies, indicating the preservation of neutralizing epitopes found in contemporary subtype B viruses. When used as DNA vaccines in guinea pigs, ConB and wild-type env immunogens induced appreciable binding, but overall only low level neutralizing antibodies. However, all four ConB immunogens were significantly more potent than one wild-type vaccine at eliciting neutralizing antibodies against a panel of tier 1 and tier 2 viruses, and ConB gp145 and gp160 were significantly more potent than both wild-type vaccines at inducing neutralizing antibodies against tier 1 viruses. Thus, consensus subtype B env immunogens appear to be at least as good as, and in some instances better than, wild-type B env immunogens at inducing a neutralizing antibody response, and are amenable to further improvement by specific gene modifications.

AIDS Vaccines↗
PubMed2006

Role of V1V2 and other human immunodeficiency virus type 1 envelope domains in resistance to autologous neutralization during clade C infection.

Biologically functional clade C envelope (Env) glycoproteins from the chronically (donor) and newly (recipient) infected partners of four heterosexual transmission pairs in Zambia were cloned and characterized previously. In each case, the donor viral quasispecies contained Envs that were resistant to autologous neutralization by contemporaneous plasma, while the recipient Envs were sensitive to neutralizing antibodies in this donor plasma sample. The donor Envs also varied in length, glycosylation, and amino acid sequence of the V1V2 hypervariable domain of gp120, while the recipient Envs were much more homogeneous. To assess the contribution of V1V2 to the neutralization phenotype of the donor Envs, V1V2 domains from neutralization-sensitive recipient Envs were replaced with donor V1V2 domains, and the autologous neutralization sensitivities of the chimeric Envs were evaluated using a virus-pseudotyping assay. Long donor V1V2 domains regulated sensitivity to autologous neutralization, although the effect was dependent on the Env background. Short donor V1V2 domains did not confer neutralization resistance. Primary sequence differences in V2 were also found to influence neutralization sensitivity in one set of recipient Envs. The results demonstrate that expansion of the V1V2 domain is one pathway to escape from autologous neutralization in subtype C Envs. However, V1V2-independent mechanisms of resistance also exist, suggesting that escape is multifaceted in chronic subtype C infection.

Autoantigens↗
PubMed2006

Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1.

High-level immune activation and T cell apoptosis represent a hallmark of HIV-1 infection that is absent from nonpathogenic SIV infections in natural primate hosts. The mechanisms causing these varying levels of immune activation are not understood. Here, we report that nef alleles from the great majority of primate lentiviruses, including HIV-2, downmodulate TCR-CD3 from infected T cells, thereby blocking their responsiveness to activation. In contrast, nef alleles from HIV-1 and a subset of closely related SIVs fail to downregulate TCR-CD3 and to inhibit cell death. Thus, Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses that likely evolved to maintain viral persistence in the context of an intact host immune system. This function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans.

Animals↗
PubMed2006

Ancestral and consensus envelope immunogens for HIV-1 subtype C.

Immunogens based on "centralized" (ancestral or consensus) HIV-1 sequences minimize the genetic distance between vaccine strains and contemporary viruses and should thus elicit immune responses that recognize a broader spectrum of viral variants. However, the biologic, antigenic and immunogenic properties of such inferred gene products have to be validated experimentally. Here, we report the construction and characterization of the first full-length ancestral (AncC) and consensus (ConC) env genes of HIV-1 (group M) subtype C. The codon-usage-optimized genes expressed high levels of envelope glycoproteins that were incorporated into HIV-1 virions, mediated infection via the CCR5 co-receptor and retained neutralizing epitopes as recognized by plasma from patients with chronic HIV-1 subtype C infection. Guinea pigs immunized with AncC and ConC env DNA developed high titer binding, but no appreciable homologous or heterologous neutralizing antibodies. When tested by immunoblot analysis, sera from AncC and ConC env immunized guinea pigs recognized a greater number of primary subtype C envelope glycoproteins than sera from guinea pigs immunized with a contemporary subtype C env control. Mice immunized with AncC and ConC env DNA developed gamma interferon T cell responses that recognized overlapping peptides from the cognate ConC and a heterologous subtype C Env control. Thus, both AncC and ConC env genes expressed functional envelope glycoproteins that were immunogenic in laboratory animals and elicited humoral and cellular immune responses of comparable breadth and magnitude. These results establish the utility of centralized HIV-1 subtype C Env immunogens and warrant their continued evaluation as potential components of future AIDS vaccines.

AIDS Vaccines↗
PubMed2006

Chimpanzee reservoirs of pandemic and nonpandemic HIV-1.

Human immunodeficiency virus type 1 (HIV-1), the cause of human acquired immunodeficiency syndrome (AIDS), is a zoonotic infection of staggering proportions and social impact. Yet uncertainty persists regarding its natural reservoir. The virus most closely related to HIV-1 is a simian immunodeficiency virus (SIV) thus far identified only in captive members of the chimpanzee subspecies Pan troglodytes troglodytes. Here we report the detection of SIVcpz antibodies and nucleic acids in fecal samples from wild-living P. t. troglodytes apes in southern Cameroon, where prevalence rates in some communities reached 29 to 35%. By sequence analysis of endemic SIVcpz strains, we could trace the origins of pandemic (group M) and nonpandemic (group N) HIV-1 to distinct, geographically isolated chimpanzee communities. These findings establish P. t. troglodytes as a natural reservoir of HIV-1.

Animals↗
PubMed2006

Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1.

Information about neutralizing antibody responses in subtype C-infected individuals is limited, even though this viral subtype causes the majority of AIDS cases worldwide. Here we compared the course and magnitude of the autologous neutralizing antibody (NAb) response against viral envelope (Env) glycoproteins present during acute and early infection with subtypes B and C human immunodeficiency virus type 1 (HIV-1). NAb responses were evaluated in 6 subtype B-infected and 11 subtype C-infected subjects over a mean evaluation period of 25 months using a pseudovirus reporter gene assay. All subjects in the C cohort were infected through heterosexual contact, while five of the six subjects in the B cohort were infected via male-to-male contact. The kinetics and magnitude of the NAb responses varied among subjects in the B and C cohorts; however, the median 50% inhibitory concentration (IC(50) titer) reached by antibody in the plasma of subtype C-infected subjects, overall, was 3.5-fold higher than in the subtype B-infected subjects (P = 0.06). The higher titers of NAbs in the C cohort were associated with viruses having significantly shorter amino acid length (P = 0.002) in the V1 to V4 region of the surface Env glycoprotein, gp120, compared to the B cohort. Despite the potency of the autologous subtype C NAb response, it was not directed against cross-neutralizing epitopes. These data demonstrate that subtype C Envs elicit a potent yet restricted NAb response early in infection that frequently reaches IC(50) titers in excess of 1:1,000 and suggest that clade-specific differences may exist in Env immunogenicity or susceptibility to neutralization.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Widely varying SIV prevalence rates in naturally infected primate species from Cameroon.

Although it is now well established that a substantial proportion of wild-living primates in sub-Saharan Africa harbor SIV, no study to date has examined to what extent the various species are naturally infected. In this study, we first describe the development and validation of sensitive and specific SIV antibody detection assays representing all major known primate lentiviral lineages on a panel of 207 sera from 11 different primate species with known infection status. The newly developed assays were then used to determine SIV prevalence rates in nine primate species native to Cameroon. Analysis of 722 sera revealed widely varying prevalence rates, ranging from an apparent absence of SIV infection in crested mona (0/70), grey cheeked (0/36) and agile mangabeys (0/92), to prevalence rates of 3%, 4%, 11%, 27%, 39% and 52% for mustached (6/203), greater spot-nosed (8/193), northern talapoin (3/26), mantled guereza (14/52), De Brazza's (9/23) and mandrill (14/27) monkeys, respectively. The epidemiology of naturally occurring SIV infections is thus more complex than previously appreciated and the various non-human primate hosts seem to differ in their susceptibility to SIV infection. The newly developed assays should now permit to define with greater accuracy existing SIV reservoirs and associated human zoonotic risk.

Amino Acid Sequence↗
PubMed2005

Antigenic conservation and immunogenicity of the HIV coreceptor binding site.

Immunogenic, broadly reactive epitopes of the HIV-1 envelope glycoprotein could serve as important targets of the adaptive humoral immune response in natural infection and, potentially, as components of an acquired immune deficiency syndrome vaccine. However, variability in exposed epitopes and a combination of highly effective envelope-cloaking strategies have made the identification of such epitopes problematic. Here, we show that the chemokine coreceptor binding site of HIV-1 from clade A, B, C, D, F, G, and H and circulating recombinant form (CRF)01, CRF02, and CRF11, elicits high titers of CD4-induced (CD4i) antibody during natural human infection and that these antibodies bind and neutralize viruses as divergent as HIV-2 in the presence of soluble CD4 (sCD4). 178 out of 189 (94%) HIV-1-infected patients had CD4i antibodies that neutralized sCD4-pretreated HIV-2 in titers (50% inhibitory concentration) as high as 1:143,000. CD4i monoclonal antibodies elicited by HIV-1 infection also neutralized HIV-2 pretreated with sCD4, and polyclonal antibodies from HIV-1-infected humans competed specifically with such monoclonal antibodies for binding. In vivo, variants of HIV-1 with spontaneously exposed coreceptor binding surfaces were detected in human plasma; these viruses were neutralized directly by CD4i antibodies. Despite remarkable evolutionary diversity among primate lentiviruses, functional constraints on receptor binding create opportunities for broad humoral immune recognition, which in turn serves to constrain the viral quasispecies.

Amino Acid Sequence↗
PubMed2005

Simian immunodeficiency virus infection in free-ranging sooty mangabeys (Cercocebus atys atys) from the Taï Forest, Côte d'Ivoire: implications for the origin of epidemic human immunodeficiency virus type 2.

Simian immunodeficiency virus of sooty mangabeys (SIVsmm) is recognized as the progenitor of human immunodeficiency virus type 2 (HIV-2) and has been transmitted to humans on multiple occasions, yet the epidemiology and genetic diversity of SIVsmm infection in wild-living populations remain largely unknown. Here, we report the first molecular epidemiological survey of SIVsmm in a community of approximately 120 free-ranging sooty mangabeys in the Taï Forest, Côte d'Ivoire. Fecal samples (n = 39) were collected from 35 habituated animals (27 females and 8 males) and tested for SIVsmm virion RNA (vRNA). Viral gag (800 bp) and/or env (490 bp) sequences were amplified from 11 different individuals (eight females and three males). Based on the sensitivity of fecal vRNA detection and the numbers of samples analyzed, the prevalence of SIVsmm infection was estimated to be 59% (95% confidence interval, 0.35 to 0.88). Behavioral data collected from this community indicated that SIVsmm infection occurred preferentially in high-ranking females. Phylogenetic analysis of gag and env sequences revealed an extraordinary degree of genetic diversity, including evidence for frequent recombination events in both the recent and distant past. Some sooty mangabeys harbored near-identical viruses (<2% interstrain distance), indicating epidemiologically linked infections. These transmissions were identified by microsatellite analyses to involve both related (mother/daughter) and unrelated individuals, thus providing evidence for vertical and horizontal transmission in the wild. Finally, evolutionary tree analyses revealed significant clustering of the Taï SIVsmm strains with five of the eight recognized groups of HIV-2, including the epidemic groups A and B, thus pointing to a likely geographic origin of these human infections in the eastern part of the sooty mangabey range.

Animals↗
PubMed2004

Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission.

Heterosexual transmission accounts for the majority of human immunodeficiency virus-1 (HIV-1) infections worldwide, yet the viral properties that determine transmission fitness or outgrowth have not been elucidated. Here we show, for eight heterosexual transmission pairs, that recipient viruses were monophyletic, encoding compact, glycan-restricted envelope glycoproteins. These viruses were also uniquely sensitive to neutralization by antibody from the transmitting partner. Thus, the exposure of neutralizing epitopes, which are lost in chronic infection because of immune escape, appears to be favored in the newly infected host. This reveals characteristics of the envelope glycoprotein that influence HIV-1 transmission and may have implications for vaccine design.

AIDS Vaccines↗
PubMed2004

Complete genome analysis of one of the earliest SIVcpzPtt strains from Gabon (SIVcpzGAB2).

Chimpanzees in west central Africa (Pan troglodytes troglodytes) are known to harbor simian immunodeficiency viruses (SIVcpzPtt) that represent the closest relatives of human immunodeficiency virus type 1 (HIV-1); however, the number of SIVcpzPtt strains that have been fully characterized is still limited. Here, we report the complete nucleotide sequence of SIVcpzGAB2, a virus originally identified in 1989 in a chimpanzee (P. t. troglodytes) from Gabon. Analysis of this sequence reveals that SIVcpzGAB2 is a member of the SIVcpzPtt group of viruses, but that it differs from other SIVcpzPtt strains by exhibiting a highly divergent Env V3 loop with an unusual crown (NLSPGTT) containing a canonical N-linked glycosylation site, an unpaired cysteine residue in Env V4, and two late (L) domain motifs (PTAP and YPSL) in Gag p6. Moreover, phylogenetic analyses indicate evidence of recombination during the early divergence of SIVcpzPtt strains; in particular, part of the pol gene sequence of SIVcpzGAB2 appears to be derived from a previously unidentified SIVcpz lineage ancestral to HIV-1 group O. These data indicate extensive diversity among naturally occurring SIVcpzPtt strains and provide new insight into the origin of HIV-1 group O.

Animals↗
PubMed2004

Nef proteins from simian immunodeficiency virus-infected chimpanzees interact with p21-activated kinase 2 and modulate cell surface expression of various human receptors.

The accessory Nef protein allows human immunodeficiency virus type 1 (HIV-1) to persist at high levels and to cause AIDS in infected humans. The function of HIV-1 group M subtype B nef alleles has been extensively studied, and a variety of in vitro activities believed to be important for viral pathogenesis have been established. However, the function of nef alleles derived from naturally simian immunodeficiency virus (SIV)-infected chimpanzees, the original host of HIV-1, or from the HIV-1 N and O groups resulting from independent zoonotic transmissions remains to be investigated. In the present study we demonstrate that SIVcpz and HIV-1 group N or O nef alleles down-modulate CD4, CD28, and class I or II MHC molecules and up-regulate surface expression of the invariant chain (Ii) associated with immature major histocompatibility complex (MHC) class II. Furthermore, the ability of Nef to interact with the p21-activated kinase 2 was generally conserved. The functional activity of HIV-1 group N and O nef genes did not differ significantly from group M nef alleles. However, SIVcpz nef genes as a group showed a 1.8- and 2.0-fold-higher activity in modulating CD28 (P = 0.0002) and Ii (P = 0.016) surface expression, respectively, but were 1.7-fold less active in down-regulating MHC class II molecules (P = 0.006) compared to HIV-1 M nef genes. Our finding that primary SIVcpz nef alleles derived from naturally infected chimpanzees modulate the surface expression of various human cellular receptors involved in T-cell activation and antigen presentation suggests that functional nef genes helped the chimpanzee virus to persist efficiently in infected humans immediately after zoonotic transmission.

Adult↗
PubMed2004

New simian immunodeficiency virus infecting De Brazza's monkeys (Cercopithecus neglectus): evidence for a cercopithecus monkey virus clade.

Nearly complete sequences of simian immunodeficiency viruses (SIVs) infecting 18 different nonhuman primate species in sub-Saharan Africa have now been reported; yet, our understanding of the origins, evolutionary history, and geographic distribution of these viruses still remains fragmentary. Here, we report the molecular characterization of a lentivirus (SIVdeb) naturally infecting De Brazza's monkeys (Cercopithecus neglectus). Complete SIVdeb genomes (9,158 and 9227 bp in length) were amplified from uncultured blood mononuclear cell DNA of two wild-caught De Brazza's monkeys from Cameroon. In addition, partial pol sequences (650 bp) were amplified from four offspring of De Brazza's monkeys originally caught in the wild in Uganda. Full-length (9068 bp) and partial pol (650 bp) SIVsyk sequences were also amplified from Sykes's monkeys (Cercopithecus albogularis) from Kenya. Analysis of these sequences identified a new SIV clade (SIVdeb), which differed from previously characterized SIVs at 40 to 50% of sites in Pol protein sequences. The viruses most closely related to SIVdeb were SIVsyk and members of the SIVgsn/SIVmus/SIVmon group of viruses infecting greater spot-nosed monkeys (Cercopithecus nictitans), mustached monkeys (Cercopithecus cephus), and mona monkeys (Cercopithecus mona), respectively. In phylogenetic trees of concatenated protein sequences, SIVdeb, SIVsyk, and SIVgsn/SIVmus/SIVmon clustered together, and this relationship was highly significant in all major coding regions. Members of this virus group also shared the same number of cysteine residues in their extracellular envelope glycoprotein and a high-affinity AIP1 binding site (YPD/SL) in their p6 Gag protein, as well as a unique transactivation response element in their viral long terminal repeat; however, SIVdeb and SIVsyk, unlike SIVgsn, SIVmon, and SIVmus, did not encode a vpu gene. These data indicate that De Brazza's monkeys are naturally infected with SIVdeb, that this infection is prevalent in different areas of the species' habitat, and that geographically diverse SIVdeb strains cluster in a single virus group. The consistent clustering of SIVdeb with SIVsyk and the SIVmon/SIVmus/SIVgsn group also suggests that these viruses have evolved from a common ancestor that likely infected a Cercopithecus host in the distant past. The vpu gene appears to have been acquired by a subset of these Cercopithecus viruses after the divergence of SIVdeb and SIVsyk.

Amino Acid Sequence↗
PubMed2004

Further investigation of simian immunodeficiency virus Vif function in human cells.

Primate lentivirus Vif proteins function by suppressing the antiviral activity of the cell-encoded apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) proteins APOBEC3G and APOBEC3F. It has been hypothesized that species-specific susceptibilities of APOBEC proteins to Vif proteins may help govern the transmission of primate lentiviruses to new host species. Consistent with this view and with previous results, we report that the Vif proteins of several diverse simian immunodeficiency viruses (SIVs) that are not known to infect humans are not effective inhibitors of human APOBEC3G or APOBEC3F when assessed in transient-transfection experiments. Unexpectedly, this lack of SIV Vif function did not prevent the replication of two vif-deficient SIVs (SIVtan and SIVmnd1; isolated from tantalus monkeys and mandrills, respectively) in a human T-cell line, HUT78, that expresses both APOBEC 3G and APOBEC3F, a finding which demonstrates that some SIVs are partially resistant to the antiretroviral effects of these enzymes irrespective of Vif function. Additional virus replication studies also revealed that the Vif protein of SIVtan is, in fact, active in human T cells, as it substantially enhanced the replication of its cognate virus and human immunodeficiency virus type 1. In sum, we now consider it improbable that species-specific restrictions to SIV Vif function can explain the lack of human infection with certain SIVs. Instead, our data reveal that the species-specific modulation of Vif function is more complex than previously envisioned and that additional (as-yet-unidentified) viral or host factors may be involved in regulating this dynamic interaction between host and pathogen.

APOBEC-3G Deaminase↗
PubMed2003

Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice.

Codon usage optimization of human immunodeficiency virus type 1 (HIV-1) structural genes has been shown to increase protein expression in vitro as well as in the context of DNA vaccines in vivo; however, all optimized genes reported thus far are derived from HIV-1 (group M) subtype B viruses. Here, we report the generation and biological characterization of codon usage-optimized gag, pol, env (gp160, gp140, gp120), and nef genes from a primary (nonrecombinant) HIV-1 subtype C isolate. After transfection into 293T cells, optimized subtype C genes expressed one to two orders of magnitude more protein (as determined by immunoblot densitometry) than the corresponding wild-type constructs. This effect was most pronounced for gp160, gp140, Gag, and Pol (>250-fold), but was also observed for gp120 and Nef (45- and 20-fold, respectively). Optimized gp160- and gp140-derived glycoproteins were processed, incorporated into virus particles, and mediated virus entry when expressed in trans to complement an env-minus HIV-1 provirus. Mice immunized with optimized gp140 DNA developed antibody as well as CD4+ and CD8+ T cell immune responses that were orders of magnitude greater than those of mice immunized with wild-type gp140 DNA. These data confirm and extend previous studies of codon usage optimization of HIV-1 genes to the most prevalent group M subtype. Our panel of matched optimized and wild-type subtype C genes should prove valuable for studies of protein expression and function, the generation of subtype-specific immunological reagents, and the production of DNA-based sub-unit vaccines directed against a broader spectrum of viruses.

AIDS Vaccines↗
PubMed2003

Noninvasive detection of Simian immunodeficiency virus infection in a wild-living L'Hoest's monkey (Cercopithecus Ihoesti).

L'Hoest's monkey's (Cercopithecus Ihoesti) are believed to be naturally infected with a simian immunodeficiency virus (SIV), termed SIVIho, but only a handful of isolates, all derived from captive animals from the Democratic Republic of Congo (DCR), have thus far been characterized. Here, we report the noninvasive detection and molecular characterization of SIVIho in a wild L'Hoest's monkey from the Nyungwe Forest in Rwanda. Screening four L'Hoest's monkey fecal samples collected opportunistically as part of a larger noninvasive survey of SIV prevalence in Nyungwe National Park we identified one to be vRNA positive. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification of a subgenomic pol fragment (598 bp) identified a new SIVIho strain (RW30) that differed from previously reported SIVIho isolates in 17-22% of its nucleotide sequence. In a phylogenic tree of partial Pol protein sequences, RW30 fell well within the SIVIho radiation, but was not particularly closely related to any of the other strains. These results provide the first direct evidence that L'Hoewst's monkeys harbor SIVIho in the wild, that infection is prevalent in different areas of the species' habitat, and that geographically diverse SIVIho strains cluster in a single group according to their species of origin. L'Hoest's monkeys represent the third primate species for which the utility of noninvasive SIV testing has been documented.

Animals↗