TABLE 2.

Amino acids characteristic of C_IN lineage and their potential evolutionary and structural significance

Subtype	n	Prevalence of CIN amino acid at Env positiona:
		290 [T]	335 [R]b	336 [A]b	340 [N]b	350 [R]	363 [K]	415 [Q]	429 [K]cd	440 [S]be
CIN	46	0.58 (Q)	0.44 (K)	0.36 (D)	0.73 (E)	0.78 (A)	0.60 (S)	0.44 (G)	0.84 (E)	0.6 (E)
Cf	146	0.65 (E)	0.30 (E)	0.15 (E)	0.46 (K)	0.30 (K)	0.59 (P)	0.32 (K)	0.46 (G)	0.44 (A)
A	177				0.18	0.01			0.00
B	234				0.06	0.00			0.65
D	104				0.02	0.00			0.35
E	91				0.66	0.00			0.08
F	25				0.04	0.00			0.20
G	91				0.60	0.03			0.00
H	13				0.15	0.00			0.00
J	2				0.00	0.00			0.00
K	6				0.00	0.00			0.17
Group O	12				0.42	0.00			0.00
CRF-AGg	54				0.09	0.00			0.00

^aPositions and letters in brackets correspond to the HXB2 prototype Env sequence (GenBank accession no. K03455). Values are prevalences of the C_IN amino acid in the indicated subtype Env sequence (except for data for subtype C; see below). In an alignment of 192 sequences, the consensus in C_IN differed from the remaining C sequences at the nine positions shown. Using a cutoff of 70%, three positions (in bold) appear to have a signature amino acid corresponding to C_IN lineage sequences. All available sequences were used for all subtypes except subtype B. 

^bSite has significantly predominant nonsynonymous substitutions indicative of positive selection acting on the site (46). 

^cSite has significantly predominant synonymous substitutions indicative of negative selection acting on the site (46). 

^dSite has been shown to interact with CD4 in the gp120 crystal structure (24). 

^eSite has been shown to interact with CCR5 in the gp120 crystal structure (37). 

^fLetters in parentheses are the residues most prevalent in non-C_IN subtype C sequences, and values in this row are prevalences of these amino acids. 

^gCirculating recombinant form comprising subtypes A and G.