Historical perspective of foamy virus epidemiology and infection

Abstract

Foamy viruses (FV) are complex retroviruses which are widespread in many species. Despite being discovered over 40 years ago, FV are among the least well characterized retroviruses. The replication of these viruses is different in many interesting respects from that of all other retroviruses. Infection of natural hosts by FV leads to a lifelong persistent infection, without any evidence of pathology. A large number of studies have looked at the prevalence of primate foamy viruses in the human population. Many of these studies have suggested that FV infections are prevalent in some human populations and are associated with specific diseases. More recent data, using more rigorous criteria for the presence of viruses, have not confirmed these studies. Thus, while FV are ubiquitous in all nonhuman primates, they are only acquired as rare zoonotic infections in humans. In this communication, we briefly discuss the current status of FV research and review the history of FV epidemiology, as well as the lack of pathogenicity in natural, experimental, and zoonotic infections.

FIG. 1

Electron microscopy of SFVcpz(hu)-infected human embryonic lung fibroblasts. (A) Preassembled core budding through the plasma membrane. (B) Preassembled cores accumulating in cytoplasm of cell and budding into intracellular membranes such as the endoplasmic reticulum. Note the spiked Env projections and the absence of further maturation of viral cores after budding through membranes. Bars, 100 μm.

FIG. 2

Schematic representation of SFVcpz(hu) genome and viral RNAs. (A) Genome of SFVcpz (hu) showing the location of gag, pol, env, tas (bel-1), bet, bel-2, and the putative bel-3 genes. Cross-hatched box indicates location of the IP. Half-arrows indicate transcription start sites for the LTR and IP. (B) Major RNAs produced in SFVcpz(hu)-infected cells. mRNAs are represented by solid lines, and ORFs are represented by rectangles. Multiple rectangles on bet mRNA indicate a spliced message.

FIG. 3

Comparison of FV and conventional retroviral life cycles. The nucleus is shown in yellow, and the endoplasmic reticulum (ER) is shown in gray. DNA genomes are represented by blue bars, and RNA genomes are represented by curved red lines. Characteristics specific to the FV life cycle are denoted by red text and arrows. Features common to both FV and conventional life cycles are shown with black text and arrows. Blue text and arrows represent events which are specific to conventional retroviruses. ^aFV and conventional type-D retroviruses assemble cores in the cytoplasm, while viruses such as HIV do not, but instead assemble at the plasma membrane. ^bFV have been shown to bud through the plasma membrane, but the majority of infectious virus buds through the endoplasmic reticulum. Processes denoted with a question mark are believed to occur, but have not been proven. The precise timing of reverse transcription is not known, but for SFVcpz(hu) it occurs late in the viral life cycle and is completed before viral adsorption.