Reverse Transcription of HIV RNA

Stable Identifier
R-HSA-162589
Type
Pathway
Species
Homo sapiens
Related Species
Human immunodeficiency virus 1
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The RNA genome of HIV-1, like that of other retroviruses, is reverse-transcribed (Baltimore 1970; Temin and Mizutani 1970) into double-stranded DNA, which is then integrated into a host cell chromosome and transcribed to yield both viral mRNAs and viral genomic RNAs. HIV-1 reverse transcription takes place in the cytosol of a newly infected host cell and involves multiple steps of RNA synthesis and degradation of the RNA strand of RNA:DNA duplexes mediated by the HIV-1 RT protein, as well as two template switches, to yield a DNA duplex colinear with the viral genomic RNA but with additional Long Terminal Repeat (LTR) sequence motifs at both ends (Telesnitsky and Goff 1997; Jonckheere et al. 2000).

HIV-1 RT has two catalytic activities essential for transcription of a DNA duplex copy of the viral genomic RNA: a reverse transcriptase activity and an RNase H activity. The reverse transcriptase is primer dependent and can transcribe both RNA and DNA templates in a 5'-3' direction. The RNaseH acts on the RNA strand of RNA:DNA duplexes and can catalyze both endo- and exonucleolytic cleavage of such an RNA strand. RT is a heterodimer of 66 and 51 kD polypeptides, both generated by cleavage of the HIV-1 Pol gene product: p66 contains Pol amino acid residues 599-1158; p51 contains residues 599-1038. Both active sites of the HIV-1 RT enzyme are contained in the p66 polypeptide, the polymerase activity in its aminoterminal region, and the RNase in its carboxyterminus. The p51 subunit lacks an RNaseH domain, and while its polymerase domain is intact, its conformation in the p66:p51 heterodimer occludes the active site (Hughes et al. 1996; Jacobo-Molina et al. 1993; Kohlstaedt et al. 1992; Wang et al. 1994).

The process of reverse transcription is outlined in the figure below: viral genomic RNA and primer tRNA are shown in black, "minus" strand DNA is shown in red, and "plus" strand DNA is shown in blue.

Literature References
PubMed ID Title Journal Year
1377403 Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor.

Kohlstaedt, LA, Wang, J, Friedman, JM, Rice, PA, Steitz, TA

Science 1992
8627740 What is the orientation of DNA polymerases on their templates?

Hughes, SH, Hostomsky, Z, Le Grice, SF, Lentz, K, Arnold, E

J Virol 1996
10723025 The HIV-1 reverse transcription (RT) process as target for RT inhibitors

Jonckheere, H, Anne, J, De Clercq, E

Med Res Rev 2000
7518928 Structural basis of asymmetry in the human immunodeficiency virus type 1 reverse transcriptase heterodimer

Wang, J, Smerdon, SJ, Jager, J, Kohlstaedt, LA, Rice, PA, Friedman, JM, Steitz, TA

Proc Natl Acad Sci U S A 1994
7687065 Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA.

Jacobo-Molina, A, Ding, J, Nanni, RG, Clark AD, Jr, Lu, X, Tantillo, C, Williams, RL, Kamer, G, Ferris, AL, Clark, P, Hizi, A, Arnold, E, Hughes, SH

Proc Natl Acad Sci U S A 1993
4316301 RNA-dependent DNA polymerase in virions of Rous sarcoma virus

Temin, HM, Mizutani, S

Nature 1970
4316300 RNA-dependent DNA polymerase in virions of RNA tumour viruses

Baltimore, D

Nature 1970
  Retroviruses

Coffin, JM, Hughes, SH, Varmus, HE

  1997
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Disease
Name Identifier Synonyms
Human immunodeficiency virus infectious disease 526 HIV infection
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