Formation of Pre-Integration Complex (PIC)

Stable Identifier
Reaction [dissociation]
Homo sapiens
Related Species
Human immunodeficiency virus 1
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Concomitant with the completion of reverse transcription, the pre-integration complex is formed by shedding of some viral proteins from the viral core, and binding of cellular proteins, thereby yielding complexes capable of integration. The terminal cleavage reaction takes place in the cytoplasm, where two nucleotides are removed from each viral DNA 3' end. This serves to remove heterogeneous extra bases from the viral DNA ends occasionally added by reverse transcription, thereby yielding a homogeneous substrate for downstream steps, and also serves to stablilize the PIC. The DNA in PICs is considerably compacted relative to its length when fully extended, probably due to binding of proteins in addition to the viral integrase. These proteins are not fully clarified, due to the difficulty of biochemical analysis of small amounts of material, but candidates include the viral NC and MA proteins, and the cellular HMGA, BAF, and PSIP1/LEDGF/p75 proteins. Purified integrase is capable of carrying out the terminal cleavage and initial strand transfer reactions.

Literature References
PubMed ID Title Journal Year
9038339 HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of preintegration complexes in vitro

Bushman, FD, Farnet, CM

Cell 1997
9188609 Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition

Miller, MD, Bushman, FD

J Virol 1997
3032450 Correct integration of retroviral DNA in vitro

Brown, PO, Varmus, HE, Bowerman, B, Bishop, JM

Cell 1987
16291214 Retroviral DNA integration--mechanism and consequences

Bushman, FD, Lewinski, MK

Adv Genet 2005
16175173 Genome-wide analysis of retroviral DNA integration

Hoffmann, C, Ciuffi, A, Leipzig, J, Hannenhalli, S, Barr, S, Bushman, FD, Lewinski, M

Nat Rev Microbiol 2005
9860958 The barrier-to-autointegration protein is a host factor for HIV type 1 integration

Engelman, A, Chen, H

Proc Natl Acad Sci U S A 1998

Varmus, HE, Hughes, SH, Coffin, JM

Name Identifier Synonyms
Human immunodeficiency virus infectious disease DOID:526 HIV infection
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