HIV-1 Protease Cleavage Sites

The protease of HIV-1 is a small 99-amino acid aspartic enzyme that mediates the cleavage of Gag, Gag-Pol and Nef precursor polyproteins. These reactions occur late in the viral life cycle, during virion assembly and maturation at the cell surface. The process is highly specific, temporally regulated and essential for the production of infectious viral particles (Jakes et al., Krausslich et al, Swanstrom et al.). In total twelve proteolytic reactions are required to generate a viable virion. Each reaction occurs at a unique cleavage site that differs in amino acid composition (Billich et al.).

Cite the resource by citing the following paper:
de Oliveira T et al. Variability at HIV-1 Subtype C Protease Cleavage Sites: An Indication of Viral Fitness? Journal of Virology (2003), 77(17): 9422-30




 

Choose the protease cleavage site for more information:

Pr55gag polyprotein clevage sites:
Pr160gag-pol polyprotein clevage sites:
Nef protein clevage sites:
1) MA/CA
6) NC/TFP
12) Nef
2) CA/p2
7) TFP/p6pol

3) p2/NC
8) p6pol/PR

4) NC/p1
9) PR/RTp51

5) p1/p6gag
10) RT/RTp66


11) RTp66/INT


Proteins Formed by Cleavage:
As shown in the above figure, the main structural proteins are formed by cleavage of the Pr55gag polyprotein into matrix (MA, p17),  capsid (CA, p24), nucleocapsid (NC, p7), p2, p1 ,p6gag.
The viral enzymes are formed by cleavage of a second polyprotein, Pr160gag-pol, a fusion protein derived by ribosomal frame shifting (13). Although Pr160gag-pol also contains p17, p24 and p2, its C-terminal cleavage products are NC, a transframe protein (TFP), p6pol, protease (PR), reverse transcriptase (RTp51), RT-RNase H (RTp66) and integrase (IN)(Ikuta et al., Tessmer et al.).



HIV-1 Protease Cleavage Site Amino Acid Sequences:
2) CA/p2 (p24/p2)

Pr55gag polyprotein clevage sites:

1)MA/CA (p17/p24)

M group MRCA
V
S
Q
N
Y
/
P
I
V
Q
N
Consensus M group
V
S
Q
N
Y
/
P
I
V
Q
N
HXB2 reference
V
S
Q
N
Y
/
P
I
V
Q
N
HXB2 numbering
Gag protein:


complete genome:


M group MRCA
K
A
R
V
L
/
A
E
A
M
S
Consensus M group
K
A
R
V
L
/
A
E
A
M
S
HXB2 reference
K
A
R
V
L
/
A
E
A
M
S
HXB2 numbering
Gag protein:


complete genome:



3) p2/NC

M group MRCA
S
T
A
I
M
/
M
Q
K
G
N
Consensus M group
x
x
A
I
M
/
M
Q
K
S
N
HXB2 reference
T
S
A
I
M
/
M
Q
R
G
N
HXB2 numbering
Gag protein:


complete genome:


4) NC/p1

M group MRCA
E
R
Q
A
N
/
F
L
G
K
I
Consensus M group
E
R
Q
A
N
/
F
L
G
K
I
HXB2 reference
E
R
Q
A
N
/
F
L
G
K
I
HXB2 numbering
Gag protein:


complete genome:


5) p1/p6gag

M group MRCA
R
P
G
N
F
/
L
Q
S
R
P
Consensus M group
R
P
G
N
F
/
L
Q
S
R
P
HXB2 reference
R
P
G
N
F
/
L
Q
S
R
P
HXB2 numbering
Gag protein:


complete genome:


6) NC/TFP

M group MRCA
E
R
Q
A
N
/
F
L
R
E
N
Consensus M group
E
R
Q
A
N
/
F
L
R
E
N
HXB2 reference
E
R
Q
A
N
/
F
L
R
E
N
HXB2 numbering
Gag protein:


complete genome:


7)TFP/p6pol

M group MRCA
E
N
L
A
F
/
Q
Q
G
E
A
Consensus M group
E
N
L
A
F
/
x
Q
G
E
A
HXB2 reference
E
D
L
A
F
/
L
Q
G
K
A
HXB2 numbering
Gag protein:


complete genome:



8)p6pol/PR

M group MRCA
T
S
F
S
F
/
P
Q
I
T
C
Consensus M group
x
S
F
x
F
/
P
Q
I
T
C
HXB2 reference
V
S
F
N
F
/
P
Q
V
T
C
HXB2 numbering
Gag protein:


complete genome:



9)PR/RTp51

M group MRCA
C
T
L
N
F
/
P
I
S
P
I
Consensus M group
C
T
L
N
F
/
P
I
S
P
I
HXB2 reference
C
T
L
N
F
/
P
I
S
P
I
HXB2 numbering
Gag protein:


complete genome:



10)RT/RTp66

M group MRCA
G
A
E
T
F
/
Y
V
D
G
A
Consensus M group
G
A
E
T
F
/
Y
V
D
G
A
HXB2 reference
G
A
E
T
F
/
Y
V
D
G
A
HXB2 numbering
Gag protein:


complete genome:



11) RTp66/INT

M group MRCA
I
R
K
V
L
/
F
L
D
G
I
Consensus M group
I
R
K
V
L
/
F
L
D
G
I
HXB2 reference
I
R
K
V
L
/
F
L
D
G
I
HXB2 numbering
Gag protein:


complete genome:



12) Nef

M group MRCA
P
D
C
A
W
/
L
E
A
Q
E
Consensus M group
x
D
C
A
W
/
L
E
A
Q
E
HXB2 reference
A
A
C
A
W
/
L
E
A
Q
E
HXB2 numbering
Gag protein:


complete genome:



References:



De Oliveira T, Engelbrecht S, Janse Van Rensburg E, Gordon M, Bishop K, Zur Megede J, Barnett SW,Cassol S. 2003. Variability at Human Immunodeficiency Virus Type 1 Subtype C Protease Cleavage Sites: an Indication of Viral Fitness?Journal of Virology 77(17): pages 9422-9430,

Ikuta, K., S. Suzuki, H. Horikoshi, T. Mukai, and R. B. Luftig. 2000. Positive and negative aspects of the human immunodeficiency virus protease: development of inhibitors versus its role in AIDS pathogenesis. Microbiol. Mol. Biol. Rev. 64:725-745.[Abstract/Free Full Text]

Jacks, T., M. D. Power, F. R. Masiarz, P. A. Luciw, P. J. Barr, H. E. Varmus. 1998. Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature 331:280-283.[CrossRef]

Krausslich, H., F. H. Ingraham, M. Skoog, E. Wimmer, P. V. Pallai, and C. A. Carter. 1989. Activity of purified biosynthetic proteinase of human immunodeficiency virus on natural substrates and synthetic peptides. Proc. Natl. Acad. Sci. USA 86:807-811.[Medline]

Swanstrom, R., and J. W. Wills. 1997. Retroviral gene expression. II. Synthesis, processing, and assembly of viral proteins, p. 263-334. In J. M. Coffin, S. H. Hughes, and H. E. Varmus (ed.), Retroviruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.


Billich, S., M. T. Knoop, J. Hansen, P. Strop, J. Sedlacek, R. Mertz, and K. Moelling. 1988. Synthetic peptides as substrates and inhibitors of human immunodeficiency virus-1 protease. J. Biol. Chem. 263:17905-17908.[Abstract/Free Full Text]


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