HIV-1 sequence evolution in vivo after superinfection with three viral strains.
With millions of people infected worldwide, the evolution of HIV-1 in vivo has been the subject of much research. Although recombinant viruses were detected early in the epidemic, evidence that HIV-1 dual infections really occurred came much later. Dual infected patients, consisting of coinfected (second infection before seroconversion) and superinfected (second infection after seroconversion) individuals, opened up a new area of HIV-1 evolution studies. Here, we describe the in-depth analysis of HIV-1 over time in a patient twice superinfected with HIV-1, first with a subtype B (B2) strain and then with CRF01_AE after initial infection with a subtype B (B1) strain. The nucleotide evolution of gag and env-V3 of the three strains followed a similar pattern: a very low substitution rate in the first 2-3 years of infection, with an increase in synonymous substitutions thereafter. Convergent evolution at the protein level was rare: only a single amino acid in a gag p24 epitope showed convergence in the subtype B strains. Reversal of CTL-epitope mutations were also rare, and did not converge. Recombinant viruses were observed between the two subtype B strains. Luciferase-assays suggested that the CRF01_AE long terminal repeat (LTR) constituted the strongest promoter, but this was not reflected in the plasma viral load. Specific real-time PCR assays based upon the env gene showed that strain B2 and CRF01_AE RNA was present in equal amounts, while levels of strain B1 were 100-fold lower. All three strains were detected in seminal plasma, suggesting that simultaneous transmission is possible.
Kozaczynska
Karolina
K
Laboratory of Experimental Virology, Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam (CINIMA), Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands. k.kozaczynska@amc.uva.nl
Cornelissen
Marion
M
Reiss
Peter
P
Zorgdrager
Fokla
F
van der Kuyl
Antoinette C
AC
D019943:Amino Acid Substitution / Q000235:genetics; D019143:Evolution, Molecular; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D016679:Genome, Viral / Q000235:genetics*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D020125:Mutation, Missense; D012367:RNA, Viral / Q000097:blood; D011995:Recombination, Genetic; D012661:Semen / Q000821:virology; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000821:virology
D015686:Gene Products, env; D015683:Gene Products, gag; D012367:RNA, Viral
Retrovirology. 2006;3:2
16398936
Nucleic Acids Res. 1992 Jan 11;20(1):27-31
1738599
AIDS Res Hum Retroviruses. 2006 Oct;22(10):968-78
17067266
J Virol. 1995 Mar;69(3):1810-8
7853521
AIDS Res Hum Retroviruses. 2004 Feb;20(2):255-8
15018715
J Virol. 1999 Aug;73(8):6810-20
10400779
Mol Biol Evol. 1993 May;10(3):512-26
8336541
J Virol. 1999 Jan;73(1):81-91
9847310
Mol Cell Biol. 1993 Sep;13(9):5691-701
8355710
AIDS. 2001 Apr 13;15(6):683-91
11371682
Gene Ther. 2006 Oct;13(19):1382-90
16724096
AIDS Res Hum Retroviruses. 2007 Mar;23(3):466-70
17411380
Prog Nucleic Acid Res Mol Biol. 1996;54:1-34
8768071
AIDS Res Hum Retroviruses. 1997 Feb 10;13(3):247-52
9115812
Immunol Today. 1984 Sep;5(9):265-8
25290326
J Virol. 1999 Dec;73(12):10489-502
10559367
Virus Genes. 2004 Apr;28(3):259-72
15266107
J Virol. 1999 Sep;73(9):7368-75
10438826
Nat Med. 2004 Mar;10(3):275-81
14966520
Mol Cell Biol. 1993 Jan;13(1):44-56
8417342
J Virol. 2005 Aug;79(16):10701-8
16051862
Nat Med. 2004 Mar;10(3):282-9
14770175
J Virol. 1997 Jun;71(6):4761-70
9151870
J Virol. 2005 Nov;79(21):13239-49
16227247
Mol Biol Evol. 2005 Mar;22(3):456-68
15509726
J Virol. 2005 Sep;79(18):11693-704
16140747
J Biol Chem. 1999 Jul 2;274(27):19434-40
10383459
AIDS Res Hum Retroviruses. 2004 May;20(5):465-75
15186520
J Acquir Immune Defic Syndr. 2006 May;42(1):12-8
16763489
Nature. 2002 Jul 11;418(6894):144
12110879
J Virol. 2005 Jul;79(13):8249-61
15956571
J Virol. 1996 Nov;70(11):8209-12
8892955
AIDS. 2006 Nov 28;20(18):2263-73
17117012
Virology. 2007 Jul 5;363(2):437-46
17336363
J Virol. 2000 Feb;74(3):1234-40
10627533
In Silico Biol. 2002;2(1):S1-15
11808873
J Virol. 2000 Jun;74(12):5679-90
10823876
J Virol. 2000 Apr;74(8):3740-51
10729149
AIDS. 2004 Jan 23;18(2):153-9
15075531
N Engl J Med. 2005 Jun 16;352(24):2557-9
15958817