Retroviridae and Human Endogenous Retroviridae
An Introduction to the Retroviridae
Plagiarized Errors and Molecular Genetics
Constructing Primate Phylogenies from Ancient Retrovirus Sequences
HERV-W
Isolation and phylogeny of endogenous retrovirus sequences belonging to the HERV-W family in primates. Heui-Soo Kim, Osamu Takenaka and Timothy J. Crow. Journal of General Virology (1999), 80, 2613–2619.
. . . The pol gene sequences of the ERV-W family were detected in hominoids and Old World monkeys, but not in New World monkeys, whereas ERV-W long terminal repeat-like elements were detected in all primates (hominoids, Old World monkeys and New World monkeys). Thirty-two pol gene sequences from hominoids and Old World monkeys showed a high degree of sequence identity to MSRV and other HERV-W sequences. Phylogenetic analysis indicated close relationships of pol gene sequences across primate species. . .
Envelope gene of the
human endogenous retrovirus HERV-W encodes a functional
retrovirus envelope. D.S. An Xie Ym I.S. Chen. JOURNAL OF
VIROLOGY Apr 2001; 75(7):3488-9
A member of the human endogenous retrovirus (HERV) family termed
HERV-W encodes a highly fusogenic membrane glycoprotein that
appears to be expressed specifically in the placenta. It is
unclear whether the glycoproteins of the HERVs can serve as
functional retrovirus envelope proteins to confer infectivity on
retrovirus particles. We found that the HERV-W envelope
glycoprotein can form pseudotypes with human immunodeficiency
virus type 1 virions and confers tropism for CD4-negative cells.
Thus, the HERV-W env gene represents the first HERV env gene
demonstrated to encode the functional properties of a retrovirus
envelope glycoprotein.
HERV-K
The HERV-K Proviruses in All Humans. M. BARBULESCU, G. TURNER, M. SU, M. SEAMAN, K. KIDD, and J. LENZ. Albert Einstein Coll. of Med., Bronx, NY; and Yale Univ. Sch. of Med., New Haven, CT. 7th Conference on Retroviruses and Opportunistic Infections, Foundation for Retrovirology and Human Health
Endogenous retroviruses contribute to the evolution of the host genome and can be associated with diseases in their hosts. Human endogenous retrovirus K (HERV-K) is related to mouse mammary tumor virus (MMTV) and is present in the genomes of catarrhines (humans, apes, and cercopithecoids (old world monkeys)). All humans have about 30 to 50 HERV-K proviruses in their germline DNA. Expression of HERV-K genes has been reported in several tissues including male germ cell tumors and normal placenta where budding viral particles can be detected. Using a BAC library, we cloned 12 distinct, full-length HERV-K proviruses from the human genome. Eight were found to be present in a genetically highly diverse set of humans but not in other extant hominoids. Intact preintegration sites for these proviruses were present in the apes. When coupled with an analysis of HERV-K solo LTRs in the human genome (Medstrand and Mager, J. Virol. 72:9782 1998), these results suggest that hundreds of HERV-K proviruses formed after humans and chimpanzees diverged in evolution, of which a subset persists today as full-length proviruses. Dating of the time of formation of individual proviruses by comparison of 5' and 3' LTR sequences suggests that most of the full-length proviruses in the human genome today formed relatively recently compared to the time of divergence of humans and chimpanzees from a common ancestor. Thus, all the viral open reading frames and cis-acting sequences necessary for HERV-K replication must have been intact throughout the recent time when these proviruses formed. Complete sequencing of seven human-specific proviruses showed that full-length open reading frames for Gag-Pro-Pol, Env, or cORF (Rev) proteins were each present in multiple proviruses. One provirus had full-length ORFs for all the viral proteins. These observations suggest that all the components necessary for HERV-K replication may be present in the human genome today. Even if none of the individual proviruses are intact, complementation among different HERV-K proviruses in the human genome may allow production of infectious viral particles. If so, then recombination may occur among functional portions of HERV-K genomes.
Human endogenous retrovirus K homologous sequences and their coding capacity in Old World primates. J. Mayer E. Meese N. Mueller-Lantzsch. JOURNAL OF VIROLOGY Mar 1998; 72(3):1870-5
The coding capacity for retroviral Gag and Env proteins has been maintained in human endogenous retroviruses of the HERV-K family. HERV- K homologous sequences have been found in all Old World primates. Here, we examined Old World primate species for the presence of full-length HERV-K gag and env genes and the presence of gag and env open reading frames as determined by the protein truncation test. Full-length HERV-K env genes were found in DNAs of all Old World primate species, whereas open reading frames for Env protein were found solely in human, chimpanzee, and gorilla DNAs. The mutational event leading to two HERV- K types was found to have occurred after the separation of hominids from lower Old World primates and before the expansion of hominids. Full-length HERV-K gag genes in hominids displayed a 96-bp deletion compared to those in lower Old World primates. The ancient gag variant has not been maintained during hominid evolution. Open reading frames for HERV-K Gag have been found in all Old World primates except chimpanzees. Our study of the HERV-K family during Old World primate evolution contributes to the understanding of their possible biological functions in the host genomes.
Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans. Curr Biol. 1999 Aug 26;9(16):861-8. Barbulescu M; Turner G; Seaman MI; Deinard AS; Kidd KK; Lenz J; Department of Molecular Genetics, Albert Einstein College of; Medicine
Endogenous retroviruses contribute to the evolution of the host genome and can be associated with disease. Human endogenous retrovirus K (HERV-K) is related to the mouse mammary tumor virus and is present in the genomes of humans, apes and cercopithecoids (Old World monkeys). It is unknown how long ago in primate evolution the full-length HERV-K proviruses that are in the human genome today were formed. RESULTS: Ten full-length HERV-K proviruses were cloned from the human genome. Using provirus-specific probes, eight of the ten were found to be present in a genetically diverse set of humans but not in other extant hominoids. Intact preintegration sites for each of these eight proviruses were present in the apes. A ninth provirus was detected in the human, chimpanzee, bonobo and gorilla genomes, but not in the orang-utan genome. The tenth was found only in humans, chimpanzees and bonobos. Complete sequencing of six of the human-specific proviruses showed that full-length open reading frames for the retroviral protein precursors Gag-Pro-Pol or Env were each present in multiple proviruses. CONCLUSIONS: At least eight full-length HERV-K genomes that are in the human germline today integrated after humans diverged from chimpanzees. All of the viral open reading frames and cis-acting sequences necessary for HERV-K replication must have been intact during the recent time when these proviruses formed. Multiple full-length open reading frames for all HERV-K proteins are present in the human genome today.
HERV-E
Structure and
phylogenetic analysis of an endogenous retrovirus inserted into
the human growth factor gene pleiotrophin. A.M. Schulte A.
Wellstein. JOURNAL OF VIROLOGY Jul 1998; 72(7):6065-72
A human endogenous retrovirus-like element (HERV), flanked by
long terminal repeats of 502 and 495 nucleotides is inserted into
the human pleiotrophin (PTN) gene upstream of the open reading
frame. Based on its Glu-tRNA primer binding site specificity and
the location within the PTN gene, we named this element HERV-E.PTN.
HERV-E.PTN appears to be a recombined viral element based on its
high homology (70 to 86%) in distinct areas to members of two
distantly related HERV type C families, HERV-E and retrovirus-like
element I (RTVL-I). Furthermore, its pseudogene region is
organized from 5' to 3' into gag-, pol-, env-, pol-, env-similar
sequences. Interestingly, full-length and partial HERV-E.PTN-homologous
sequences were found in the human X chromosome, the human
hereditary haemochromatosis region, and the BRCA1 pseudogene.
Finally, Southern analyses indicate that the HERV-E.PTN element
is present in the PTN gene of humans, chimpanzees, and gorillas
but not of rhesus monkeys, suggesting that genomic insertion
occurred after the separation of monkeys and apes about 25
million years ago.
HERV-F
Using primers from a conserved region of the XA34 human endogenous retrovirus (HERV) family, four pol fragments originating from new members of the family were amplified from human genomic DNA. Southern blot analysis demonstrated similar hybridization patterns in human, chimpanzee and orangutan and distinct hybridization to macaque DNA. The probes also exhibited weaker hybridization to squirrel monkey DNA. Using large genomic clones, two full-length XA34-related HERVs have been identified. One of the HERVs is located downstream of a human Krüppel-related zinc finger protein gene, ZNF195. Both of the newly identified long terminal repeats have potential TATA boxes, poly(A) signals and transcription factor-binding sites but they differ to a high degree, especially in the U3 region. The primer-binding sites were found to be homologous to tRNAPhe (TTC), and therefore these new HERVs have been given the name HERV-F. The closest relatives to the HERV-Fs are the RTVLH-RGH family. Phylogenetic analyses of the Gag, Pol and Env regions are discussed. Both of the newly identified HERV-Fs were shown to contain protease, reverse transcriptase, integrase and env regions and had characteristic deletions in the integrase and env regions. In addition, the capsid protein gene of gag and two conserved zinc-binding motifs that are characteristic of a potential nucleic acid-binding protein were also identified. Apart from an ORF spanning the protease of one HERV-F, no other longer ORFs were found.
HERV-IP-T47D
HERV-IP-T47D, a novel type C-related human endogenous retroviral sequence derived from T47D particles. W. Seifarth C. Baust U. Schȵn A. Reichert R. Hehlmann C. Leib-Mȵsch. AIDS RESEARCH AND HUMAN RETROVIRUSES Mar 20, 2000; 16(5):471-80.
A new type C retrovirus-related endogenous pol sequence (ERV-FTD) found to be occasionally copackaged in retrovirus-like particles released by the human mammary carcinoma cell line T47D was used to screen a human genomic library (Seifarth W, Skladny H, Krieg-Schneider F, Reichert A, Hehlmann R, and Leib-Mȵsch C: J Virol 1995;69:6408-6416). The DNA sequence of one full-length clone now reveals a human endogenous proviral sequence (HERV) of 4190 bp in length comprising a 5' LTR (489 bp) and regions with 37 and 74% overall amino acid homology to RTVL-Ia gag and pol genes, respectively. About 35 related elements were found to be distributed on all human chromosomes except 16, 17, and Y. Sequence comparisons with Mo-MuLV and various type C-related HERVs suggest that despite a proline primer-binding site this novel HERV element, now named HERV-IP-T47D, can be assigned to one family together with known HERV-I elements. Phylogenetic analyses of 5 proviral and 25 solitary LTR sequences confirmed the existence of two distinct but closely related subgroups of the HERV-IP superfamily in the primate genome. In contrast to most known HERV-families, the evolutionary age of HERV-IP elements dates back prior to the divergence of New and Old World monkeys. Despite their old age, members of the HERV-IP family are still transcriptionally active and were found to be highly expressed in specific human tissues such as liver and kidney.
Dangel, A. W., B. J. Baker, A.
R. Mendoza, and C. Y. Yu. 1995. Complement component C4 gene
intron 9 as a phylogenetic marker for primates: long terminal
repeats of the endogenous retrovirus ERV-K(C4) are a molecular
clock of evolution. Immunogenetics. 42(1):41-52.
The complement component C4 genes of Old World primates exhibit a
long/short dichotomous size variation, except that chimpanzee
and gorilla only contain short C4 genes. In human it has been
shown that the long C4 gene is attributed to the integration of
an endogenous retrovirus, HERV-K(C4), into intron 9. This
6.36 kilobase retroviral element is absent in short C4 genes.
Here it is shown that the homologous endogenous retrovirus, ERV-K(C4),
is present precisely at the same position in the long C4 gene of
orangutan and African green monkey. Determination of the short C4
gene intron 9 sequences from human, three apes, two Old World
monkeys, and a New World monkey allowed the establishment of
consistent phylogenetic trees for primates, which favors a chimpanzee-gorilla
clade. The 5' long terminal repeats (LTR) and 3' LTR of ERV-K(C4)
in long C4 genes of human, orangutan, and African green monkey
have similar sequence divergence values of 9.1%-10.5%. These
values are more than five-fold higher than the sequence
divergence of the homologous intron 9 sequences between the long
and short C4 genes in higher primates. The latter is probably a
result of homogenization or concerted evolution. We suggest that
the 5' LTR and 3' LTR of an endogenous retrovirus can serve as a
reliable reference point or a molecular clock for studies of gene
duplication and gene evolution. This is because the 5'/3' LTR
sequences were identical at the time of retroviral integration
and evolved independently of each other afterwards. Our data
provides strong evidence for the short C4 gene being the
ancestral form in primates, trans-species evolution, and the
"slow-down" phenomenon of the sequence divergence in
great apes.