Characterization of human endogenous retroviral elements in the blood of HIV-1-infected individuals.
We previously reported finding the RNA of a type K human endogenous retrovirus, HERV-K (HML-2), at high titers in the plasma of HIV-1-infected and cancer patients (R. Contreras-Galindo et al., J. Virol. 82:9329-9236, 2008.). The extent to which the HERV-K (HML-2) proviruses become activated and the nature of their activated viral RNAs remain important questions. Therefore, we amplified and sequenced the full-length RNA of the env gene of the type 1 and 2 HERV-K (HML-2) viruses collected from the plasma of seven HIV-1-infected patients over a period of 1 to 3 years and from five breast cancer patients in order to reconstruct the genetic evolution of these viruses. HERV-K (HML-2) RNA was found in plasma fractions of HIV-1 patients at a density of ∼1.16 g/ml that contained both immature and correctly processed HERV-K (HML-2) proteins and virus-like particles that were recognized by anti-HERV-K (HML-2) antibodies. RNA sequences from novel HERV-K (HML-2) proviruses were discovered, including K111, which is specifically active during HIV-1 infection. Viral RNA arose from complete proviruses and proviruses devoid of a 5' long terminal repeat, suggesting that the expression of HERV-K (HML-2) RNA in these patients may involve sense and antisense transcription. In HIV-1-infected individuals, the HERV-K (HML-2) viral RNA showed evidence of frequent recombination, accumulation of synonymous rather than nonsynonymous mutations, and conserved N-glycosylation sites, suggesting that some of the HERV-K (HML-2) viral RNAs have undergone reverse transcription and are under purifying selection. In contrast, HERV-K (HML-2) RNA sequences found in the blood of breast cancer patients showed no evidence of recombination and exhibited only sporadic viral mutations. This study suggests that HERV-K (HML-2) is active in HIV-1-infected patients, and the resulting RNA message reveals previously undiscovered HERV-K (HML-2) genomic sequences.
Department of Internal Medicine, and Programs in Cancer Biology, Immunology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA.
Rafael
R
Contreras-Galindo
Mark H
MH
Kaplan
Angie C
AC
Contreras-Galindo
Marta J
MJ
Gonzalez-Hernandez
Ilaria
I
Ferlenghi
Fabiola
F
Giusti
Eric
E
Lorenzo
Scott D
SD
Gitlin
Michael H
MH
Dosik
Yasuhiro
Y
Yamamura
David M
DM
Markovitz
D020077:Endogenous Retroviruses / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016679:Genome, Viral; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D048348:Reverse Transcription; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus