Simian Foamy Virus Prevalence in Macaca mulatta and Zookeepers

Abstract Because of their genetic and biological similarity to humans, non-human primates are the best pre-clinical models for testing the efficacy and safety of gene therapy systems. However, the presence of endogenous simian foamy virus infection in nearly all non-human primates kept in captivity complicates foamy virus (FV) vector stem cell transduction studies in these animals. A major concern is that repopulating cells exposed to FV vector stocks will elicit an immune response in non-human primate hosts. Though human serum does not inactivate prototype foamy virus (PFV) vectors, a one hour incubation of PFV vector stock in the presence of serum samples from Papio Cynophalus (baboon), Macaca Mulatta (rhesus macaque), or Macaca Fasicularis (long-tailed macaque) results in a 75–100% drop in titer. To overcome this serum mediated inactivation we sought to pseudotype PFV vectors in the feline foamy virus (FFV) envelope. The wild-type envelope from the FUV strain of FFV does not pseudotype our PFV vectors. Therefore we generated chimeras with regions of both the FFV and PFV envelope. By substituting portions of the FFV envelope leader peptide sequence and membrane spanning domain with corresponding PFV envelope regions we generated chimeric envelopes capable of high titer (105–106 FFU/ml) PFV vector production. Serum samples from Macaca Mulatta produced less inactivation of the FFV pseudotyped than the PFV pseudotyped vectors. Furthermore, both the PFV and FFV pseudotyped vectors demonstrated efficient transduction of baboon mesenchymal stem cells (27–43%) and baboon embryonic stem cells (37–40%). However, the FFV pseudotyped vectors transduced both human and baboon CD34+ cells less efficiently than the PFV pseudotyped vectors. We plan to test PFV vectors pseudotyped by other FV envelopes for inactivation by primate serum, and for their ability to transduce primate hematopoietic cells.

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Nonhuman primate retroviruses from Cambodia: High simian foamy virus prevalence, identification of divergent STLV-1 strains and no evidence of SIV infection

Infection Genetics and Evolution ◽

10.1016/j.meegid.2013.04.015 ◽

2013 ◽

Vol 18 ◽

pp. 325-334 ◽

Cited By ~ 13

Author(s):

Ahidjo Ayouba ◽

Linda Duval ◽

Florian Liégeois ◽

Sopheak Ngin ◽

Steve Ahuka-Mundeke ◽

...

Keyword(s):

Nonhuman Primate ◽

Foamy Virus ◽

Simian Foamy Virus ◽

Virus Prevalence ◽

Siv Infection

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Contemporary Distribution, Estimated Age, and Prehistoric Migrations of Old World Monkey Retroviruses

Epidemiologia ◽

10.3390/epidemiologia2010005 ◽

2021 ◽

Vol 2 (1) ◽

pp. 46-67

Author(s):

Antoinette C. van der Kuyl

Keyword(s):

Close Contact ◽

World Monkey ◽

Foamy Virus ◽

Endogenous Retrovirus ◽

Papio Cynocephalus ◽

Endogenous Virus ◽

Simian Foamy Virus ◽

Old World ◽

T Lymphotropic Virus ◽

Type D

Old World monkeys (OWM), simians inhabiting Africa and Asia, are currently affected by at least four infectious retroviruses, namely, simian foamy virus (SFV), simian immunodeficiency virus (SIV), simian T-lymphotropic virus (STLV), and simian type D retrovirus (SRV). OWM also show chromosomal evidence of having been infected in the past with four more retroviral species, baboon endogenous virus (BaEV), Papio cynocephalus endogenous virus (PcEV), simian endogenous retrovirus (SERV), and Rhesus endogenous retrovirus-K (RhERV-K/SERV-K1). For some of the viruses, transmission to other primates still occurs, resulting, for instance, in the HIV pandemic. Retroviruses are intimately connected with their host as they are normally spread by close contact. In this review, an attempt to reconstruct the distribution and history of OWM retroviruses will be made. A literature overview of the species infected by any of the eight retroviruses as well as an age estimation of the pathogens will be given. In addition, primate genomes from databases have been re-analyzed for the presence of endogenous retrovirus integrations. Results suggest that some of the oldest retroviruses, SERV and PcEV, have travelled with their hosts to Asia during the Miocene, when a higher global temperature allowed simian expansions. In contrast, younger viruses, such as SIV and SRV, probably due to the lack of a primate continuum between the continents in later times, have been restricted to Africa and Asia, respectively.

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Simian Foamy Virus Transmission from Apes to Humans, Rural Cameroon

Emerging Infectious Diseases ◽

10.3201/eid1309.061162 ◽

2007 ◽

Vol 13 (9) ◽

pp. 1314-1320 ◽

Cited By ~ 80

Author(s):

Sara Calattini ◽

Edouard B.A. Betsem ◽

Alain Froment ◽

Philippe Mauclère ◽

Patricia Tortevoye ◽

...

Keyword(s):

Foamy Virus ◽

Virus Transmission ◽

Simian Foamy Virus ◽

Rural Cameroon

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Identification of a Conserved Residue of Foamy Virus Gag Required for Intracellular Capsid Assembly

Journal of Virology ◽

10.1128/jvi.75.15.6857-6864.2001 ◽

2001 ◽

Vol 75 (15) ◽

pp. 6857-6864 ◽

Cited By ~ 47

Author(s):

Scott W. Eastman ◽

Maxine L. Linial

Keyword(s):

Foamy Virus ◽

Specific Interaction ◽

Capsid Assembly ◽

Particle Assembly ◽

Simian Foamy Virus ◽

Viral Budding ◽

Extracellular Release ◽

Infected Cells ◽

Targeting Signal ◽

Strict Requirement

ABSTRACT In contrast to all retroviruses but similar to the hepatitis B virus, foamy viruses (FV) require expression of the envelope protein for budding of intracellular capsids from the cell, suggesting a specific interaction between the Gag and Env proteins. Capsid assembly occurs in the cytoplasm of infected cells in a manner similar to that for the B- and D-type viruses; however, in contrast to these retroviruses, FV Gag lacks an N-terminal myristylation signal and capsids are not targeted to the plasma membrane (PM). We have found that mutation of an absolutely conserved arginine (Arg) residue at position 50 to alanine (R50A) of the simian foamy virus SFV cpz(hu) inhibits proper capsid assembly and abolishes viral budding even in the presence of the envelope (Env) glycoproteins. Particle assembly and extracellular release of virus can be restored to this mutant with the addition of an N-terminal Src myristylation signal (Myr-R50A), presumably by providing an alternate site for assembly to occur at the PM. In addition, the strict requirement of Env expression for capsid budding can be bypassed by addition of a PM-targeting signal to Gag. These results suggest that intracellular capsid assembly may be mediated by a signal akin to the cytoplasmic targeting and retention signal CTRS found in Mason-Pfizer monkey virus and that FV Gag has the inherent ability to assemble capsids at multiple sites like conventional retroviruses. The necessity of Env expression for particle egress is most probably due to the lack of a membrane-targeting signal within FV Gag to direct capsids to the PM for release and indicates that Gag-Env interactions are essential to drive particle budding.

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