Persistent asymptomatic infection of the laboratory mouse by simian foamy virus type 6: A new model of retrovirus latency

Brown, Paul; Moreau-Dubois, M C; Gajdusek, D. Carleton

doi:10.1007/bf01314874

Cited by 20 publications

(13 citation statements)

References 9 publications

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“…While full BFV repli- cation and reisolation of replication-competent virus from experimentally infected calves was anticipated, reisolation of BFV from infected sheep at 3 years p.i. clearly confirms for the first time that BFV can also replicate in a heterologous host species, as previously observed for other FVs (44,45,46,47). In addition, BFV was rescued from both infected animal hosts even in the presence of BFV-specific antibodies, confirming that BFV infection is not cleared by the host immune system.…”

Section: Discussionsupporting

confidence: 67%

Similar Patterns of Infection with Bovine Foamy Virus in Experimentally Inoculated Calves and Sheep

Materniak

Hechler

Löchelt

et al. 2013

J Virol

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bFoamy viruses (FVs) are the least known retroviruses commonly found in primates, cats, horses, and cattle. Although FVs are considered apathogenic, simian and feline FVs have been shown to be associated with some transient health abnormalities in animal models. Currently, data regarding the course of infection with bovine FV (BFV) are not available. In this study, we conducted experimental infections of natural (cattle) and heterologous (sheep) hosts with the BFV 100 isolate and monitored infection patterns in both hosts during the early phase postinoculation as well as after long-term infection. Four calves and six sheep inoculated with BFV 100 showed no signs of pathology but developed persistent infection, as confirmed by virus rescue, consistent detection of BFV-specific antibodies, and presence of viral DNA. In both hosts, antibodies against BFV Gag and Bet appeared early after infection and persisted at high and stable levels while seroreactivity toward Env was consistently detectable only in BFV-infected sheep. Interestingly, the BFV proviral DNA load was highest in lung, spleen, and liver and moderate in leukocytes, while salivary glands contained either low or undetectable DNA loads in calves or sheep, respectively. Additionally, comparison of partial BFV sequences from inoculum and infected animals demonstrated very limited changes after long-term infection in the heterologous host, clearly less than those found in BFV field isolates. The persistence of BFV infection in both hosts suggests full replication competence of the BFV 100 isolate with no requirement of genetic adaptation for productive replication in the authentic and even in a heterologous host.

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Section: Discussionsupporting

confidence: 67%

Similar Patterns of Infection with Bovine Foamy Virus in Experimentally Inoculated Calves and Sheep

Materniak

Hechler

Löchelt

et al. 2013

J Virol

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“…One defining characteristic of in vivo FV infection is the lack of detectable viral replication despite the ability to recover virus by coculturing of infected tissues with susceptible cells in vitro (6,7,9,11,38,41,42,53). The reason for this characteristic is unknown but is likely to be complex.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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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“…However, this was disputed by Brown and colleagues (74,75), who failed to detect markers of HFV infection in people from any of these areas.…”

Section: Human Foamy Virusmentioning

confidence: 95%

Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic Disease

Voisset

Weiss

Griffiths

2008

Microbiol Mol Biol Rev

145

156

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SUMMARY Retroviruses are an important group of pathogens that cause a variety of diseases in humans and animals. Four human retroviruses are currently known, including human immunodeficiency virus type 1, which causes AIDS, and human T-lymphotropic virus type 1, which causes cancer and inflammatory disease. For many years, there have been sporadic reports of additional human retroviral infections, particularly in cancer and other chronic diseases. Unfortunately, many of these putative viruses remain unproven and controversial, and some retrovirologists have dismissed them as merely “human rumor viruses.” Work in this field was last reviewed in depth in 1984, and since then, the molecular techniques available for identifying and characterizing retroviruses have improved enormously in sensitivity. The advent of PCR in particular has dramatically enhanced our ability to detect novel viral sequences in human tissues. However, DNA amplification techniques have also increased the potential for false-positive detection due to contamination. In addition, the presence of many families of human endogenous retroviruses (HERVs) within our DNA can obstruct attempts to identify and validate novel human retroviruses. Here, we aim to bring together the data on “novel” retroviral infections in humans by critically examining the evidence for those putative viruses that have been linked with disease and the likelihood that they represent genuine human infections. We provide a background to the field and a discussion of potential confounding factors along with some technical guidelines. In addition, some of the difficulties associated with obtaining formal proof of causation for common or ubiquitous agents such as HERVs are discussed.

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Persistent asymptomatic infection of the laboratory mouse by simian foamy virus type 6: A new model of retrovirus latency

Cited by 20 publications

References 9 publications

Similar Patterns of Infection with Bovine Foamy Virus in Experimentally Inoculated Calves and Sheep

Similar Patterns of Infection with Bovine Foamy Virus in Experimentally Inoculated Calves and Sheep

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

Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic Disease

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