Transient immunosuppressive effect induced in rabbits and mice by the human spumaretrovirus prototype HFV (human foamy virus)

Santillana-Hayat, Maud; Rozain, Francis; Bittoun, Patricia; Chopin-Robert, C.; Lasneret, J; Périès, J.; Canivet, M

doi:10.1016/s0923-2516(06)80054-3

Cited by 22 publications

(13 citation statements)

References 18 publications

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“…The FFV vectors can be directly derived from the parental vector genomes, grown to reasonable titers in vitro, and given to the vaccinee without negative side effects. No obvious immunosuppressive effect as described for human FV infections of rabbits was detectable in our system (27).…”

Section: Discussionmentioning

confidence: 49%

“…Several features of the biology and replication strategy of FVs are advantageous with respect to the employment of replication-competent FV-based vectors. Most importantly, the lifelong persistent FV infection is considered apathogenic in the natural host and accidentally SFV-infected humans (1,16,17,21), although a slightly higher incidence of feline FV (FFV) infections in cats with uncharacterized renal symptoms and a transient immunosuppression in primate FVinfected rabbits have been reported (27,37). The prevalence of FFV in outgrown domestic cats is about 50% or higher, whereas kittens have a lower incidence of FFV infection (37), a feature that allows FFV-based vaccination early in vivo.…”

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confidence: 99%

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Application of Chimeric Feline Foamy Virus-Based Retroviral Vectors for the Induction of Antiviral Immunity in Cats

Schwantes

Truyen

Weikel

et al. 2003

J Virol

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In order to define the potential and applicability of replication-competent foamy virus-based vaccine vectors, recombinant feline foamy virus (FFV) vectors encoding defined segments of the feline calicivirus (FCV) capsid protein E domain were constructed. In cell cultures, these FFV-FCV vectors efficiently transduced and expressed a hybrid fusion protein consisting of the essential FFV Bet protein and the attached FCV E domains. The stability of the vectors in vitro was inversely correlated to the size of the heterologous insert. The deletion of a part of the FFV U3 sequence in these FFV-FCV vectors did not interfere with replication and titer in cell cultures but increased the genetic stability of the hybrid vectors. Selected chimeric vectors were injected into immunocompetent cats and persisted in the transduced host concomitant with a strong and specific humoral immune response against vector components. In a substantial number of cats, antibodies directed against the FCV E domain were induced by the FFV-FCV vectors, but no FCV-neutralizing activities were detectable in vitro. When the vaccinated cats were challenged with a high-titer FCV dose, sterile immunity was not induced by any of the hybrid FFV-FCV vectors. However, the FFV-FCV vector with a truncated U3 region of the long terminal repeat promoter significantly reduced the duration of FCV shedding after challenge and suppressed the appearance of FCV-specific ulcers. Possible mechanisms contributing to the partial protection will be discussed.The great success of applied virology during the last century has been mainly due to the development and application of efficient and safe antiviral vaccines. These prevent virus-mediated disease or spread of the infectious agent and have even resulted in the eradication of poxvirus (reviewed in reference 7). These achievements are on one hand based on the injection of defined virus-derived proteins, as in the case of the hepatitis B virus vaccine or inactivated viruses, which are both capable of inducing a stable and broadly reactive humoral immunity. Alternatively, attenuated, apathogenic virus variants and/or related viruses inducing a stable cross-protection are used. Modified live virus vaccines have the great advantage of mimicking the natural route and mode of virus replication, inducing not only a humoral, mainly immunoglobulin G (IgG)-mediated immunity, but also stimulating the cell-mediated and/or mucosal arm of the adaptive immune response (7). Although these strategies have been efficient in controlling various viruses pathogenic to humans and livestock animals, vaccines against some virus infections are presently either not available or display only a limited degree of protection (23).Over the last several years, novel vaccination strategies have been developed based on recombinant, chimeric viruses used to deliver and efficiently express heterologous vaccine antigens in the recipient (28). These novel strategies include not only prophylactic preexposure vaccination but also therapeutic postexposure im...

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Section: Discussionmentioning

confidence: 49%

mentioning

confidence: 99%

Application of Chimeric Feline Foamy Virus-Based Retroviral Vectors for the Induction of Antiviral Immunity in Cats

Schwantes

Truyen

Weikel

et al. 2003

J Virol

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“…Infection is characterized by the presence of viral DNA in a large number of organs (9, 42), without detectable levels of viral RNA or protein expression (6,9,42,44). Indeed, viral transcription has been detected only in the oral mucosa of a single infected animal (9).…”

Section: Sfvcpz(hu) (New Name For Human Fv) Ltr Promoter However Mumentioning

confidence: 99%

“…Indeed, viral transcription has been detected only in the oral mucosa of a single infected animal (9). However, virus can be recovered readily by coculturing of infected tissues, peripheral blood, or throat swab specimens with susceptible cell lines (6,18,42,44,46,49). Thus, in most locations in vivo, FV replication is latent; however, when the virus is removed from such a context, replication can proceed.…”

Section: Sfvcpz(hu) (New Name For Human Fv) Ltr Promoter However Mumentioning

confidence: 99%

Cell-Type-Specific Regulation of the Two Foamy Virus Promoters

Meiering

Rubio

May

et al. 2001

J Virol

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The foamy virus (FV) genome contains two promoters, the canonical long terminal repeat (LTR) promoter, containing three consensus AP-1 binding sites, and an internal promoter (IP) within the env gene. We investigated the regulation of the two promoters in lytic and persistent infections and found that in the presence of a constitutive source of the viral transactivator protein Tas, transactivation of the LTR promoter and that of the IP differ. In lytic infections, both the LTR promoter and the IP are efficiently transactivated by Tas, while in persistent infections, the IP is efficiently transactivated by Tas, but the LTR promoter is not. Analysis of proteins expressed from the LTR promoter and the IP during infection indicated that IP transcription is more robust than that of the LTR promoter in persistently infected cells, while the opposite is true for lytically infected cells. Coculture experiments also showed that LTR promoter transcription is greatest in cells which support lytic replication. Replacement of much of the LTR promoter with the IP leads to increased viral replication in persistent but not lytic infections. We also found that the induction of persistently infected cells with phorbol 12-myristate 13-acetate (PMA) greatly enhanced viral replication and transcription from the SFVcpz(hu) (new name for human FV) LTR promoter. However, mutation of three consensus AP-1 binding sites in the FV LTR promoter did not affect viral replication in lytically or persistently infected cells, nor did the same mutations affect LTR promoter transactivation by Tas in PMA-treated cells. Our data indicate that differential regulation of transcription is important in the outcome of FV infection but is unlikely to depend on AP-1.Foamy viruses (FVs) are unique among retroviruses in their establishment of life-long persistent infections without any accompanying pathologies. Infection is characterized by the presence of viral DNA in a large number of organs (9, 42), without detectable levels of viral RNA or protein expression (6,9,42,44). Indeed, viral transcription has been detected only in the oral mucosa of a single infected animal (9). However, virus can be recovered readily by coculturing of infected tissues, peripheral blood, or throat swab specimens with susceptible cell lines (6,18,42,44,46,49). Thus, in most locations in vivo, FV replication is latent; however, when the virus is removed from such a context, replication can proceed. In contrast to the in vivo situation, FV replication in vitro can result in either lytic or persistent infection (13,41,53). Infection of many cell types in vitro is often accompanied by cytopathic effects (CPE) and rapid cell killing. Since such infections do not mimic the in vivo situation, we sought to develop a tissue culture system in which there is little viral replication. For these studies we used the prototypic human FV (HFV) clone HFV13 (29). HFV has recently been renamed SFVcpz(hu) to more clearly indicate that the original HFV isolate is a chimpanzee FV isolated from a huma...

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“…Concerning pathogenicity, foamy virus infection of rabbits and mice however gave rise to a mild transient immunosuppressive effect, which regressed within 30 d. 60,61 In transgenic mice them the 2F5 epitope (unpublished). Studies on the neutralizing activity of these antibodies are in progress.…”

Section: Toward a Replication Competent Vaccine Virus Based On Foamy mentioning

confidence: 99%

Immunising with the transmembrane envelope proteins of different retroviruses including HIV-1

Denner

2013

Human Vaccines & Immunotherapeutics

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Transient immunosuppressive effect induced in rabbits and mice by the human spumaretrovirus prototype HFV (human foamy virus)

Cited by 22 publications

References 18 publications

Application of Chimeric Feline Foamy Virus-Based Retroviral Vectors for the Induction of Antiviral Immunity in Cats

Application of Chimeric Feline Foamy Virus-Based Retroviral Vectors for the Induction of Antiviral Immunity in Cats

Cell-Type-Specific Regulation of the Two Foamy Virus Promoters

Immunising with the transmembrane envelope proteins of different retroviruses including HIV-1

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