ERVs: Rabbit endogenous lentivirus K (RELIK)


Rabbit endogenous lentivirus K (RELIK) is an endogenous retrovirus (ERV) lineage derived from a lentivirus, identified in the genome of the European rabbit. This discovery provided the first insights into the ancient history of the Lentivirus genus. Molecular clock-based calibrations, applied to pairs of segmentally duplicated RELIK insertions, demonstrate that RELIK entered the lagomorph germline at least 6 million years ago.

In spite of its ancient origin, RELIK exhibits many of the features found in present day lentiviruses, such as tat and rev genes for the regulation of viral gene expression.

A hare

A startled-looking European hare (Lepus europaeus), photographed in Scotland by Andy Parkinson.

A follow-up study demonstrated the presence of lentivirus insertions in a wide range of lagomorph species, showing that invasion of the lagomorph germline by lentiviruses took place prior to the divergence of rabbits and hares ~12 million year ago.

The absence of RELIK insertions from the genome of the American pika (Ochotona princeps) indicates that genome invasion occurred after the divergence of leporids and pikas ~25 million years ago.

Links to related data items:


ERVs: Prosimian immunodeficiency viruses (PSIVs)


The human immunodeficiency viruses HIV-1 and HIV-2 are human lentiviruses that arose through cross-species transmission from primates. It is well established that these transmission events occurred in West and Central Africa, where lentiviruses are known to circulate among wild apes and monkeys. However, it has generally been assumed that natural lentivirus infections of primates are restricted to the African mainland. s

In direct contradiction of this notion, we identified an endogenous lentivirus in the genome of a Malagasy primate - the grey mouse lemur (Microcebus murinus - pictured). Grey mouse lemur prosimian immunodeficiency virus (PSIVgml) was identified by in silico screening of whole genome sequence data, and contains some derived features, such as a vif gene, but lacks certain genes found in simian lentiviruses, such as vpr. PSIVgml is also phylogenetically intermediate, grouping between the feline and simian immunodeficiency viruses in trees.

Lemurs

Lemurs - photographs from Duke Lemur Center.

The discovery of PSIVgml is striking, because all lemurs are restricted to Madagascar - an ancient island that has been colonized by only a small number of mammalian groups since it formed approximately 200 million years ago. This unique biogeographic history is reflected in the astonishing (and sadly endangered) Malagasy primate fauna, consisting of numerous, morphologically diverse lemur species all of which are thought to have descended from a single founder population that first reached Madagascar over 60 million years ago.

In order for lentiviruses to also reach Madagascar, they must either have been present in this founder population of lemurs, or have been introduced via cross-species transmission from a non-primate species that colonised the island at a later date. Since at least one of these scenarios has to be correct, lentiviruses are either (i) more transmissible between species groups, or (ii) far older than has previously been recognised.

As such, it is possible that lentiviral infections afflict, or have afflicted, primate populations throughout the world. Uncharacterised primate lentiviruses might represent a potential source of new human infections, but could also provide valuable new model systems for studying HIV/AIDS.

Links to related data items:


Lentivirus-GLUE: Highlights


These highlights pages aim to provide a brief overview of selected data items contained within the Lentivirus-GLUE project, and to illustrate how it can be used to implement reproducible comparative analyses.

XRVs: Equine infectious anemia virus


Equine infectious anaemia virus (EIAV) is a lentivirus that infects horses worldwide. In a collaborative investigation of genetic diversity among globally sampled EIAV isolates we found clear evidence of geographic compartmentalization, with distinct strains being predominant in Asia, Europe and the Americas. In addition, our study found evidence that the majority EIAV strain found in the Americas originated approximately 400 years ago - around the time that horses were reintroduced to the New World by European colonists.

Equids became extinct in the Americas ~12,500 years ago, and were not re-introduced until the late 15th Century. Prior to the development of reliable serologic tests in the early 1970s, it was virtually impossible to distinguish inapparent carriers of EIAV from uninfected animals and European colonists likely introduced the disease to the Americas unwittingly.

New World viruses analyzed in the study were sampled in countries throughout the Americas, including sites in Argentina, Canada and the USA. The predominance of a single, distinct EIAV strain suggests that a small number of ancestral 'founder' strains gave rise to the main EIAV epidemic in the New World.


The North-Western periphery of Europe

The wild horses of Shackleford Banks: "They've always been here - they swam ashore off sinking ships."

Importantly, the study included a sample obtained from a horse belonging to the Shackleford Banks wild herd. The Shackleford Banks wild horses occupy an isolated barrier island in North Carolina, USA. They are a unique breed, thought to be descended from animals abandoned by Spanish explorers in the early part of the 16th century, after failed attempts to colonize the Atlantic coastal regions of North America.

Phylogenetic trees place the EIAV strain found in Shackleford Banks horses in an ancestral position relative to other New World isolates, consistent with EIAV having been introduced by early European colonists.



Related Publications


Gifford RJ (2012)
Viral evolution in deep time - Lentiviruses and mammals.
Trends in Genetics [view]

Capomaccio S, Cappelli K, Cook RF, Nardi F, Gifford RJ, Marenzoni ML, and F. Passamonti (2011)
Geographic structuring of global EIAV isolates: A single origin for New World strains?
Virus Research [view]

Gilbert C, Maxfield DG, Goodman SM, and Feschotte C. (2009) Parallel germline infiltration of a lentivirus in two Malagasy lemurs. PLoS Genet. [view]

Gifford RJ, Katzourakis A, Tristem M, Pybus, OG, Winters M, and RW. Shafer. (2008) A transitional endogenous lentivirus from the genome of a basal primate and implications for lentivirus evolution.
PNAS [view]

Katzourakis A, Tristem M, Pybus OG, and RJ. Gifford (2007) Discovery and analysis of the first endogenous lentivirus. PNAS [view]

Reina R, Mora MI, Glaria I, García I, Solano C, Luján L, Badiola JJ, Contreras A, Berriatua E, Juste R, Mamoun RZ, Rolland M, Amorena B, and de Andrés D. (2004) Phylogenetic analysis and reclassification of caprine and ovine lentiviruses based on 104 new isolates: evidence for regular sheep-to-goat transmission and worldwide propagation through livestock trade. Virology [abstract]