Human endogenous retrovirus family HERV-K(HML-2) RNA transcripts are selectively packaged into retroviral particles produced by the human germ cell tumor line Tera-1 and originate mainly from a provirus on chromosome 22q11.21.
The human germ cell tumor line Tera-1 produces retroviral particles which are encoded by the human endogenous retrovirus family HERV-K(HML-2). We show here, by quantitative reverse transcriptase PCR, that HML-2 gag and env RNA transcripts are selectively packaged into Tera-1 retroviral particles, whereas RNAs from cellular housekeeping genes and from other HERV families (HERV-H and HERV-W) are nonselectively copackaged. Assignment of cloned HML-2 gag and env cDNAs from Tera-1 retroviral particles to individual HML-2 loci in the human genome demonstrated that HML-2 RNA transcripts packaged into Tera-1 retroviral particles originate almost exclusively from an HML-2 provirus on chromosome 22q11.21. Based on relative cloning frequencies, this provirus was the most active among a total of eight transcribed HML-2 loci identified in Tera-1 cells. These data suggest that at least one HML-2 element, that is, the HML-2 provirus on 22q11.21, has retained the capacity for packaging RNA into HML-2-encoded retroviral particles. Given its elevated transcriptional activity and the presence of a full-length Gag open reading frame, the 22q11.21 HML-2 provirus may also significantly contribute to Gag protein and thus particle production in Tera-1 cells. Our findings provide important clues to the generation and biological properties of HML-2-encoded particles. In addition, copackaging of non-HML-2 HERV transcripts in HML-2-encoded particles should inform the debate about endogenous retroviral particles putatively encoded by non-HML-2 HERV families that have previously been described for other human diseases, such as multiple sclerosis.
Ruprecht
Klemens
K
Institut für Virologie, Universitätsklinikum des Saarlandes, Haus 47, 66421 Homburg/Saar, Germany. klemens.ruprecht@uniklinikum-saarland.de
Ferreira
Humberto
H
Flockerzi
Aline
A
Wahl
Silke
S
Sauter
Marlies
M
Mayer
Jens
J
Mueller-Lantzsch
Nikolaus
N
D045744:Cell Line, Tumor; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics / Q000821:virology; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011533:Proviruses / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly; D016662:Virus Integration
D012367:RNA, Viral