Evolutionary gamut of in vivo Gag substitutions during early HIV-1 subtype C infection.
Two analyses of HIV-1 subtype C Gag quasispecies were performed in a prospective cohort of 42 acutely and recently infected individuals by SGA on viral RNA/proviral DNA templates. First, in vivo Gag substitutions were assessed in relation to the HIV-1C consensus sequence, which revealed that 29.3% of detected amino acid substitutions can be classified as reversions to subtype consensus, 61.3% as forward substitutions from subtype consensus, and 9.3% as polymorphisms not associated with the subtype consensus sequence. Second, the proportion, dynamics, and relationships within individual pools of viral quasispecies were analyzed. Among reverse substitutions, 16.1% were minor, 11.0% transient, 13.6% dominant, and 59.2% fixed. In contrast, 31.6% of forward substitutions were minor, 59.3% transient, 3.8% dominant, and 5.3% fixed. The distinct patterns in the spectrum and dynamics of reverse and forward Gag substitutions suggest that these differences should be considered in HIV-1 evolutionary studies and analyses of viral mutational pathways.
Harvard School of Public Health AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, United States.
Vladimir
V
Novitsky
Rui
R
Wang
Jeannie
J
Baca
Lauren
L
Margolin
Mary F
MF
McLane
Sikhulile
S
Moyo
Erik
E
van Widenfelt
Joseph
J
Makhema
M
M
Essex
D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D015331:Cohort Studies; D018984:Epitopes, T-Lymphocyte; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017423:Sequence Analysis, RNA; D013602:T-Lymphocytes, Cytotoxic; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D054301:gag Gene Products, Human Immunodeficiency Virus