The V1 region of gp120 is preferentially selected during SIV/HIV transmission and is indispensable for envelope function and virus infection.
A transmission bottleneck occurs during each human immunodeficiency virus (HIV) transmission event, which allows only a few viruses to establish new infection. However, the genetic characteristics of the transmitted viruses that are preferentially selected have not been fully elucidated. Here, we analyzed amino acids changes in the envelope protein during simian immunodeficiency virus (SIV)/HIV deep transmission history and current HIV evolution within the last 15-20 years. Our results confirmed that the V1V2 region of gp120 protein, particularly V1, was preferentially selected. A shorter V1 region was preferred during transmission history, while during epidemic, HIV may evolve to an expanded V1 region gradually and thus escape immune recognition. We then constructed different HIV-1 V1 mutants using different HIV-1 subtypes to elucidate the role of the V1 region in envelope function. We found that the V1 region, although highly variable, was indispensable for virus entry and infection, probably because V1 deletion mutants exhibited impaired processing of gp160 into mature gp120 and gp41. Additionally, the V1 region affected Env incorporation. These results indicated that the V1 region played a critical role in HIV transmission and infection.
Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
Yanpeng
Y
Li
Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45122, Essen, Germany.
Ulf
U
Dittmer
Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
Yan
Y
Wang
Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
Jiping
J
Song
Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. sunbl@wh.iov.cn.
Binlian
B
Sun
Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. ryang@wh.iov.cn.
Rongge
R
Yang
D000818:Animals; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015498:HIV-2 / Q000235:genetics / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C059761:HIV envelope protein gp120 (135-148); D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C514793:gp120 protein, Human immunodeficiency virus 1; C069623:gp120 protein, Simian immunodeficiency virus; C514787:gp41 protein, Human immunodeficiency virus 1
Env function; V1 loop; human immunodeficiency virus (HIV); selection; simian immunodeficiency virus (SIV); transmission