Novel Endogenous Retrovirus in Rabbits Previously Reported as Human Retrovirus 5

Abstract

Human retrovirus 5 (HRV-5) represented a fragment of a novel retrovirus sequence identified in human RNA and DNA preparations. In this study, the genome of HRV-5 was cloned and sequenced and integration sites were analyzed. Using PCR and Southern hybridization, we showed that HRV-5 is not integrated into human DNA. A survey of other species revealed that HRV-5 is present in the genomic DNA of the European rabbit (Oryctolagus cuniculus) and belongs to an endogenous retrovirus family found in rabbits. The presence of rabbit sequences flanking HRV-5 proviruses in human DNA extracts suggested that rabbit DNA was present in our human extracts, and this was confirmed by PCR analysis that revealed the presence of rabbit mitochondrial DNA sequences in four of five human DNA preparations tested. The origin of the rabbit DNA and HRV-5 in human DNA preparations remains unclear, but laboratory contamination cannot explain the preferential detection of HRV-5 in inflammatory diseases and lymphomas reported previously. This is the first description of a retrovirus genome in rabbits, and sequence analysis shows that it is related to but distinct from A-type retroelements of mice and other rodents. The species distribution of HRV-5 is restricted to rabbits; other species, including other members of the order Lagomorpha, do not contain this sequence. Analysis of HRV-5 expression by Northern hybridization and reverse transcriptase PCR indicates that the virus is transcribed at a low level in many rabbit tissues. In light of these findings we propose that the sequence previously designated HRV-5 should now be denoted RERV-H (for rabbit endogenous retrovirus H).

Pushing the envelope: Advances in molecular techniques for the detection of novel viruses

“…The fact that scenarios similar to the XMRV story have been reported before (Griffiths et al, 2002) highlights the need for caution when implying disease causation by a novel virus. The advent of next generation sequencing technologies will increase the likelihood of such reports, as the sheer volume of sequence data generated and sensitivity of the technique makes it more likely that contaminants or non-significant virus sequences will be amplified.…”

Rabbit endogenous retrovirus-H encodes a functional protease FN1

“…The RERV-H family appears to be restricted to the European rabbit because the genomes of related members of the order Lagomorpha, including hares and pikas, do not contain RERV-H (Griffiths et al, 2002). This observation, together with the conservation of open reading frames (ORFs) for gag, pro and pol, indicates that this virus entered the rabbit genome relatively recently in evolution and raises the possibility that it is still active and infectious.…”

“…RERV-H was first identified in human tissues by PCR and RT-PCR, and was originally thought to be a novel human retrovirus, denoted human retrovirus-5 (HRV-5) (Griffiths et al, 1997). However, despite having many characteristics of infectious retroviruses, in particular an apparent association with inflammatory diseases and lymphoma (Rigby et al, 1998;Brand et al, 1999;Griffiths et al, 1999;Murovska et al, 2000;Kozireva et al, 2001), cloning of the HRV-5 genome and of some viral integration sites revealed the true origin of this virus and led to its re-designation as RERV-H (Griffiths et al, 2002).…”

“…Rabbit endogenous retrovirus-H (RERV-H) is a recently characterized endogenous retrovirus family of the European rabbit (Oryctolagus cuniculus) (Griffiths et al, 2002). RERV-H was first identified in human tissues by PCR and RT-PCR, and was originally thought to be a novel human retrovirus, denoted human retrovirus-5 (HRV-5) (Griffiths et al, 1997).…”

A new human retrovirus associated with prostate cancer

“…In other studies, retroviral sequences (initially designated human retrovirus-5) could be PCR-amplified from various human tissues, but they were ultimately found to represent an ERV of rabbits (15). The possibility that expression of HERVs may contribute to tumors has also been considered.…”