Table 1.

Mutated nef alleles and respective effects on CD4/MHC class I down-regulation, based on currently available data


Allele

Mutation

Amino acid position

Affected domain (function)

CD4*

MHC-1*

Reference
NA-7   WT   None   None   +   +   Schwartz et al,24  
NL4-3        Mariani and Skowronski27  
LAI        
LAI   G2A   Gly2   Myristoylation (membrane anchoring)   +/-   -   Aiken et al28  
NL4-3   WLAA   Trp-Leu57-58   CD4 binding site, HIV-1 protease cleavage site   -   +   Mangasarian et al29  
NL4-3   E4A   Glu-Glu-Glu-Glu62-63-64-65   PACS-1 binding site   +   -   Piguet et al30  
NA-7   PPAA   Pro72, Pro75   Polyproline helix type II (SH3 domain binding surface, interaction with Vav)   +   +/-   Saksela et al,31  
LAI        Greenberg et al32  
NA-7   D86A   Asp86   SH3 binding site   +   +   Greenberg et al,33  
       Iafrate et al34  
NL4-3   R106A   Arg106   PAK2 association   +   +/-   Iafrate et al,34  Sawai et al,35  present study  
LAI   D123G   Asp123   Oligomerization   -   -   Liu et al36  
NA-7   LLAA   Leu-Leu164-165   Clathrin adaptor interaction site   -   +   Greenberg et al,32  
LAI   LLGG       Bresnahan et al,37  
       Craig et al38  
NA-7   DALLAA   Asp86, Leu-Leu164-165   SH3 binding site, clathrin adaptor interaction site   -   +   Present study  
NA-7   EDAA   Glu-Asp174-175   Vacuolar ATPase interaction site   -   +   Iafrate et al,34  
LAI   DDGA   Asp-Asp 174-175      Aiken et al39  
NA-7
 
DAEDAA
 
Asp86, Glu-Asp174, 175
 
SH3 binding site, vacuolar ATPase interaction site
 
-
 
+
 
Present study
 

Allele

Mutation

Amino acid position

Affected domain (function)

CD4*

MHC-1*

Reference
NA-7   WT   None   None   +   +   Schwartz et al,24  
NL4-3        Mariani and Skowronski27  
LAI        
LAI   G2A   Gly2   Myristoylation (membrane anchoring)   +/-   -   Aiken et al28  
NL4-3   WLAA   Trp-Leu57-58   CD4 binding site, HIV-1 protease cleavage site   -   +   Mangasarian et al29  
NL4-3   E4A   Glu-Glu-Glu-Glu62-63-64-65   PACS-1 binding site   +   -   Piguet et al30  
NA-7   PPAA   Pro72, Pro75   Polyproline helix type II (SH3 domain binding surface, interaction with Vav)   +   +/-   Saksela et al,31  
LAI        Greenberg et al32  
NA-7   D86A   Asp86   SH3 binding site   +   +   Greenberg et al,33  
       Iafrate et al34  
NL4-3   R106A   Arg106   PAK2 association   +   +/-   Iafrate et al,34  Sawai et al,35  present study  
LAI   D123G   Asp123   Oligomerization   -   -   Liu et al36  
NA-7   LLAA   Leu-Leu164-165   Clathrin adaptor interaction site   -   +   Greenberg et al,32  
LAI   LLGG       Bresnahan et al,37  
       Craig et al38  
NA-7   DALLAA   Asp86, Leu-Leu164-165   SH3 binding site, clathrin adaptor interaction site   -   +   Present study  
NA-7   EDAA   Glu-Asp174-175   Vacuolar ATPase interaction site   -   +   Iafrate et al,34  
LAI   DDGA   Asp-Asp 174-175      Aiken et al39  
NA-7
 
DAEDAA
 
Asp86, Glu-Asp174, 175
 
SH3 binding site, vacuolar ATPase interaction site
 
-
 
+
 
Present study
 

PACS-1 indicates phosphofurin acidic cluster sorting protein-1; PAK2, p21-activated kinase 2; ATPase, adenosine triphosphatase.

*

+ indicates down-regulation; +/-, partial down-regulation; and -, no down-regulation.

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