Compositional Similarities between the Human Immunodeficiency Virus and Surface Antigens of Pathogens

Abstract

The genome of the human immunodeficiency virus (HIV) is rich in A but not U and deficient in C but not G. This asymmetric nucleotide bias is the major factor in determining the unusual composition of HIV proteins. In this report, we have identified the cellular genes in the GenBank database that are compositionally similar to HIV in order to further understand the significance of the nucleotide bias of the viral genome. A total of 101 genes in the bacterial and invertebrate subdivisions of the database were found to have a base composition that is similar to the composition of the HIV genome. The identified cellular sequences represent a discrete subset of the database since 81 of the 101 entries code for antigens from pathogens and nearly all of these organisms infect humans. The amino acid compositions of these surface antigens are also similar to the unusual composition of HIV proteins, which are deficient in proline and rich in lysine and other polar residues encoded by A-rich codons. The similarities between the HIV proteins and the immunodominant antigens from other pathogens may indicate a common pathogenic strategy for the promotion of immune dysregulation.

Exploitation of the Low Fidelity of Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase and the Nucleotide Composition Bias in the HIV-1 Genome To Alter the Drug Resistance Development of HIV

“…It is also noteworthy that erratic hypermutability has been observed not only with other lentiviruses (i.e., caprine arthritisencephalitis virus) (40) but also with nonlentiviruses, such as hepatitis B virus (20), bacteria, and protozoa (13). Therefore, our observations may be seen in a much broader context than HIV and may be applied to several other human pathogens.…”

“…The process operating over time could be responsible for the A richness of the lentiviral genome. The silent codon sites in HIV-1 are highly A rich (51%) and more deficient in G (13%) than in C (17%), and the composition of these sites should more closely reflect the true mutational bias of the genome (13). The compositional nucleotide bias of the HIV genome favors G-A transitions over T-C transitions (8), and the results presented here suggest that the normal in vivo direction of this transition is from G to A since it was observed in the presence of a variety of agents (i.e., mycophenolic acid, 2Ј-deoxycoformycin, and hydroxyurea) that do not influence the intracellular pool of dCTP.…”

“…HIV type 1 (HIV-1) appears to be among the most rapidly evolving genetic elements known, and the A-biased genome seems to have the potential to contribute to this process (2,8,9,13). The bias may also play a role in producing the surprisingly large proportion of nucleotide substitutions that cause amino acid changes in HIV proteins (30), since it favors G-A transitions over T-C transitions, which tend to promote interchanges among polar residues encoded by A-and AG-rich codons.…”

“…Such replacements are expected to have minimal deleterious effects on protein function and consequently should produce large numbers of viable variants in the population. Genes that encode antigens (virulence factors) for many bacterial, protozoan, and metazoan pathogens also display the unusual A bias, which is reflected in the composition of the encoded proteins, making it likely that diverse pathogens employ similar mechanisms for the generation of variation (13). The G3A hypermutability has been explained by the asymmetric endogenous deoxynucleotide triphosphate (dNTP) pools, with the dCTP and dGTP pools being the lowest and the dCTP/dTTP ratios being on the order of 1:2 to 1:6 (28).…”

Proline Residues within Spacer Peptide p1 Are Important for Human Immunodeficiency Virus Type 1 Infectivity, Protein Processing, and Genomic RNA Dimer Stability

“…Gag region is rich in this amino acid, which is surprising in a virus where proline residues are relatively uncommon (11). Two additional p1 mutants were created.…”