Simian Foamy Viruses: Infections in Human and Nonhuman Primate Hosts

Abstract

Foamy viruses are ancient and ubiquitous retroviruses that infect a variety of mammalian hosts. In this chapter, we focus on foamy viruses that infect nonhuman primates (NHP), called simian foamy viruses or SFV. Natural SFV infection in monkeys and apes leads to life-long, persistent infections with no associated pathogenicity. Although SFV have coevolved with their natural hosts and show strong cospeciation, there are also many examples of cross-species transmission events. SFV are transmitted primarily via saliva, and humans who come into contact with NHP saliva can become zoonotically infected with SFV. To date, SFV from a variety of NHP species have been transmitted to humans and, as seen in natural infections, there is no pathogenicity associated with these zoonotic infections. However, as in the case of other retroviruses, such as lentiviruses, it is possible that an SFV viral variant could emerge as a human pathogen. The molecular features of SFV, the situations that lead to SFV zoonotic infections, and the implications of these infections are discussed in the global context of the monkey–human interface.

Glossary

Acquired immunity:

The development of specific antibodies upon exposure to a pathogen or foreign agent, through vaccination or infection. After infection with a virus, individuals often produce antibodies to the virus that did not exist before infection and are adapted to better respond to subsequent infections with the same virus.

Antibodies:

Proteins produced by host B cells that can bind to and inactivate (neutralize) pathogens such as viruses or bacteria.

Bet:

A foamy virus accessory protein of unknown function that is not found in virus particles. Foamy viruses lacking Bet can replicate but not as well as the wild type.

Buccal swabs:

A noninvasive technique used to collect samples from an individual’s inner cheek, which will include host cell DNA as well as foamy viruses.

Complex retrovirus:

A retrovirus that encodes the highly conserved Gag, Pol, and Env protein products, as well as additional accessory proteins with various functions.

Env:

A retroviral-encoded protein found in the outer layer of a virus particle. It is used to bind viral receptors present on the host cell surface.

Foamy virus:

A complex retrovirus whose virion contains prominent spikes on the surface and a central but uncondensed core. Although RNA is packaged, reverse transcription occurs during virus assembly, leading to infectious virions containing DNA genomes.

Gag:

A retroviral-encoded protein that forms the viral capsid.

Innate immunity:

Nonspecific defense mechanisms present in host organisms prior to infection by viruses or other pathogens. These responses develop soon after infection and do not adapt to the pathogen over time.

Internal promoter (IP):

A foamy virus-specific sequence located at the 3′ end of the envelope gene required for transcription of the accessory genes tas and bet. All other retroviral genomes only contain one promoter located in the 5′ LTR.

Latent infection:

This occurs when a viral genome is maintained within a host cell but it is dormant and does not produce new viruses.

Lentivirus:

A complex retrovirus with cylindrical or conical virion cores. Their RNA genomes express gag, pro, pol, and env genes, as well as accessory genes. Some lentiviruses are highly pathogenic, such as HIV-1.

LTR:

A long terminal repeat sequence, found at both ends of an integrated retroviral genome. The 5’LTR contains DNA promoter sequences required for transcription of the viral genome while the 3’LTR contains the termination and the poly-adenylation signals.

NHP:

Nonhuman primate

NWM :

New World monkeys, found in Central and South America.

Orthoretrovirus:

A subfamily of the Retrovirus family that include most retroviruses. These viruses all have RNA genomes.

OWM :

Old World monkeys, found in Asia and Africa.

PBMC:

Peripheral blood mononuclear cells; these are nucleated cells found in blood and include lymphocytic cells such as T and B cells and monocytic cells, such as macrophages.

PCR:

Polymerase chain reaction is a technique that allows a researcher to detect, amplify, and sequence DNA. This method amplifies target DNA sequences at least a thousand times to allow easy manipulation.

Persistent infection:

An infection that lasts for a long period of time and is not cleared by host antibodies.

Pol:

A retroviral-encoded polymerase that has reverse transcriptase activity to synthesize DNA from RNA.

Productive infection:

An infection by a virus, or other microorganism, that allows the virus to replicate and produce infectious progeny. Viral productive infections are often pathogenic.

Promoter:

A DNA sequence that allows RNA polymerase to initiate transcription.

Retroviruses:

A family of viruses that generally contain a plus-strand viral RNA genome in the virus particles. A retrovirus also encodes an enzyme called reverse transcriptase that converts the viral genomic RNA into double-stranded DNA. Using another viral enzyme, called integrase, the resulting DNA is integrated permanently into a host cell chromosome. Retroviruses are divided into two subfamilies: Spumaretrovirus and Orthoretrovirus.

Reverse transcriptase:

An enzyme, encoded by retroviruses, that uses an RNA molecule to synthesize DNA.

SIV:

Simian immunodeficiency virus is a lentivirus highly related to HIV that naturally infects some African monkeys. It is not found in Asian OWM or NWM .

Spumaretrovirus:

A subfamily of the Retrovirus family that include viruses that contain DNA genomes. The only well-characterized Spumaretrovirus is the foamy virus.

Tas:

Trans activator protein produced by foamy viruses to increase RNA transcription from the viral promoters. The Tas protein is an accessory protein not found in foamy virus particles.

Transient infection:

An infection that only lasts for a limited time, usually the host immune response clears the virus.

Viral recombination:

The production of a viral genome containing information from more than one parental virus. In a population of viruses, individual virus particles can differ in their genomic sequences (viral variants). If a cell is infected by more than one viral variant, interactions between variants can occur so that new variants are produced that contain genetic information from both parental viruses.

Virus Receptor:

A host cell molecule, usually a cell membrane-associated protein, which viruses use in order to bind to and enter host cells.

Western blot:

A technique that allows a researcher to determine the presence and size of a protein(s) that react with a specific antibody. Samples containing proteins are separated by size, immobilized on a membrane, and exposed to antibodies for detection.

Zoonotic infection:

A human infection produced by a microbe that naturally infects nonhuman hosts.