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Published in: BMC Infectious Diseases 1/2020

Open Access 01-12-2020 | Human Immunodeficiency Virus | Research article

Defective HIV-1 envelope gene promotes the evolution of the infectious strain through recombination in vitro

Authors: Huamian Wei, Danwei Yu, Xiuzhu Geng, Yuxian He

Published in: BMC Infectious Diseases | Issue 1/2020

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Abstract

Background

HIV-1 produces defective mutants in the process of reproduction. The significance of the mutants has not been well investigated.

Methods

The plasmids of wild type (HIV-1NL4–3) and Env-defective (HIV-1SG3ΔEnv) HIV-1 were co-transfected into HEK293T cells. The progeny virus was collected to infect MT4 cells. The env gene and near-full-length genome (NFLG) of HIV-1 were amplified and sequenced. The phylogenetic diversity, recombinant patterns and hotspots, and the functionality of HIV-1 Env were determined.

Results

A total of 42 env genes and 8 NFLGs were successfully amplified and sequenced. Five types of recombinant patterns of env were identified and the same recombinant sites were detected in different patterns. The recombination hotspots were found distributing mainly in conservative regions of env. The recombination between genes of HIV-1NL4–3 and HIV-1SG3Δenv increased the variety of viral quasispecies and resulted in progeny viruses with relative lower infectious ability than that of HIVNL4–3. The defective env genes as well as NFLG could be detected after 20 passages.

Conclusion

The existence of the defective HIV-1 promotes the phylogenetic evolution of the virus, thus increasing the diversity of virus population. The role of defective genes may be converted from junk genes to useful materials and cannot be neglected in the study of HIV-1 reservoir.
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Literature
1.
2.
go back to reference Abram ME, Ferris AL, Das K, Quinones O, Shao W, Tuske S, Alvord WG, Arnold E, Hughes SH. Mutations in HIV-1 reverse transcriptase affect the errors made in a single cycle of viral replication. J Virol. 2014;88(13):7589–601.PubMedPubMedCentralCrossRef Abram ME, Ferris AL, Das K, Quinones O, Shao W, Tuske S, Alvord WG, Arnold E, Hughes SH. Mutations in HIV-1 reverse transcriptase affect the errors made in a single cycle of viral replication. J Virol. 2014;88(13):7589–601.PubMedPubMedCentralCrossRef
3.
go back to reference Sanchez G, Xu XY, Chermann JC, Hirsch I. Accumulation of defective viral genomes in peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected individuals. J Virol. 1997;71(3):2233–40.PubMedPubMedCentralCrossRef Sanchez G, Xu XY, Chermann JC, Hirsch I. Accumulation of defective viral genomes in peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected individuals. J Virol. 1997;71(3):2233–40.PubMedPubMedCentralCrossRef
4.
go back to reference Schwartz DH, Viscidi R, Laeyendecker O, Song HF, Ray SC, Michael N. Predominance of defective proviral sequences in an HIV plus long-term non-progressor. Immunol Lett. 1996;51(1–2):3–6.PubMedCrossRef Schwartz DH, Viscidi R, Laeyendecker O, Song HF, Ray SC, Michael N. Predominance of defective proviral sequences in an HIV plus long-term non-progressor. Immunol Lett. 1996;51(1–2):3–6.PubMedCrossRef
5.
go back to reference Bruner KM, Murray AJ, Pollack RA, Soliman MG, Laskey SB, Capoferri AA, Lai J, Strain MC, Lada SM, Hoh R, et al. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat Med. 2016;22(9):1043.PubMedPubMedCentralCrossRef Bruner KM, Murray AJ, Pollack RA, Soliman MG, Laskey SB, Capoferri AA, Lai J, Strain MC, Lada SM, Hoh R, et al. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat Med. 2016;22(9):1043.PubMedPubMedCentralCrossRef
6.
go back to reference Quan Y, Liang C, Brenner BG, Wainberg MA. Multidrug-resistant variants of HIV type 1 (HIV-1) can exist in cells as defective Quasispecies and be rescued by Superinfection with other defective HIV-1 variants. J Infect Dis. 2009;200(9):1479–83.PubMedCrossRef Quan Y, Liang C, Brenner BG, Wainberg MA. Multidrug-resistant variants of HIV type 1 (HIV-1) can exist in cells as defective Quasispecies and be rescued by Superinfection with other defective HIV-1 variants. J Infect Dis. 2009;200(9):1479–83.PubMedCrossRef
7.
go back to reference Kim EY, Busch M, Abel K, Fritts L, Bustamante P, Stanton J, Lu D, Wu S, Glowczwskie J, Rourke T, et al. Retroviral recombination in vivo: viral replication patterns and genetic structure of simian immunodeficiency virus (SIV) populations in rhesus macaques after simultaneous or sequential intravaginal inoculation with SIVmac239 Delta vpx/Delta vpr and SIVmac239 Delta nef. J Virol. 2005;79(8):4886–95.PubMedPubMedCentralCrossRef Kim EY, Busch M, Abel K, Fritts L, Bustamante P, Stanton J, Lu D, Wu S, Glowczwskie J, Rourke T, et al. Retroviral recombination in vivo: viral replication patterns and genetic structure of simian immunodeficiency virus (SIV) populations in rhesus macaques after simultaneous or sequential intravaginal inoculation with SIVmac239 Delta vpx/Delta vpr and SIVmac239 Delta nef. J Virol. 2005;79(8):4886–95.PubMedPubMedCentralCrossRef
9.
go back to reference Cooper TF. Recombination speeds adaptation by reducing competition between beneficial mutations in populations of Escherichia coli. PLoS Biol. 2007;5(9):1899–905.CrossRef Cooper TF. Recombination speeds adaptation by reducing competition between beneficial mutations in populations of Escherichia coli. PLoS Biol. 2007;5(9):1899–905.CrossRef
10.
go back to reference Immonen TT, Conway JM, Romero-Severson EO, Perelson AS, Leitner T. Recombination Enhances HIV-1 Envelope Diversity by Facilitating the Survival of Latent Genomic Fragments in the Plasma Virus Population. PLoS Comput Biol. 2015;11(12):e1004625. Immonen TT, Conway JM, Romero-Severson EO, Perelson AS, Leitner T. Recombination Enhances HIV-1 Envelope Diversity by Facilitating the Survival of Latent Genomic Fragments in the Plasma Virus Population. PLoS Comput Biol. 2015;11(12):e1004625.
11.
go back to reference Arrildt KT, Joseph SB, Swanstrom R. The HIV-1 Env protein: a coat of many colors. Curr Hiv-Aids Rep. 2012;9(1):52–63.CrossRef Arrildt KT, Joseph SB, Swanstrom R. The HIV-1 Env protein: a coat of many colors. Curr Hiv-Aids Rep. 2012;9(1):52–63.CrossRef
12.
go back to reference Shankarappa R, Margolick JB, Gange SJ, Rodrigo AG, Upchurch D, Farzadegan H, Gupta P, Rinaldo CR, Learn GH, He X, et al. Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. J Virol. 1999;73(12):10489–502.PubMedPubMedCentralCrossRef Shankarappa R, Margolick JB, Gange SJ, Rodrigo AG, Upchurch D, Farzadegan H, Gupta P, Rinaldo CR, Learn GH, He X, et al. Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. J Virol. 1999;73(12):10489–502.PubMedPubMedCentralCrossRef
13.
go back to reference Wang Z, Pan QH, Gendron P, Zhu WJ, Guo F, Cen S, Wainberg MA, Liang C. CRISPR/Cas9-derived mutations both inhibit HIV-1 replication and accelerate viral escape. Cell Rep. 2016;15(3):481–9.PubMedCrossRef Wang Z, Pan QH, Gendron P, Zhu WJ, Guo F, Cen S, Wainberg MA, Liang C. CRISPR/Cas9-derived mutations both inhibit HIV-1 replication and accelerate viral escape. Cell Rep. 2016;15(3):481–9.PubMedCrossRef
14.
go back to reference Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, Rabson A, Martin MA. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986;59(2):284–91.PubMedPubMedCentralCrossRef Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, Rabson A, Martin MA. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986;59(2):284–91.PubMedPubMedCentralCrossRef
15.
go back to reference Wei XP, Decker JM, Wang SY, Hui HX, Kappes JC, Wu XY, Salazar-Gonzalez JF, Salazar MG, Kilby JM, Saag MS, et al. Antibody neutralization and escape by HIV-1. Nature. 2003;422(6929):307–12.PubMedCrossRef Wei XP, Decker JM, Wang SY, Hui HX, Kappes JC, Wu XY, Salazar-Gonzalez JF, Salazar MG, Kilby JM, Saag MS, et al. Antibody neutralization and escape by HIV-1. Nature. 2003;422(6929):307–12.PubMedCrossRef
16.
go back to reference Wei H, Xing H, Hsi JH, Jia M, Feng Y, Duan S, He C, Yao S, Ruan Y, He X, et al. The sexually driven epidemic in youths in China's southwestern border region was caused by dynamic emerging multiple recombinant HIV-1 strains. Sci Rep. 2015;5:11323.PubMedPubMedCentralCrossRef Wei H, Xing H, Hsi JH, Jia M, Feng Y, Duan S, He C, Yao S, Ruan Y, He X, et al. The sexually driven epidemic in youths in China's southwestern border region was caused by dynamic emerging multiple recombinant HIV-1 strains. Sci Rep. 2015;5:11323.PubMedPubMedCentralCrossRef
17.
go back to reference Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol. 2010;59(3):307–21.PubMedCrossRef Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol. 2010;59(3):307–21.PubMedCrossRef
18.
go back to reference Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, Ray SC. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol. 1999;73(1):152–60. Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, Ray SC. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol. 1999;73(1):152–60.
19.
go back to reference Song HS, Giorgi EE, Ganusov VV, Cai FP, Athreya G, Yoon H, Carja O, Hora B, Hraber P, Romero-Severson E, et al. Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection. Nat Commun. 2018;9(1):1928. Song HS, Giorgi EE, Ganusov VV, Cai FP, Athreya G, Yoon H, Carja O, Hora B, Hraber P, Romero-Severson E, et al. Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection. Nat Commun. 2018;9(1):1928.
20.
go back to reference Ding XH, Zhang XJ, Chong HH, Zhu YM, Wei HM, Wu XY, He JS, Wang XQ, He YX. Enfuvirtide (T20)-Based Lipopeptide Is a Potent HIV-1 Cell Fusion Inhibitor: Implications for Viral Entry and Inhibition. J Virol. 2017;91(18):e00831-17. Ding XH, Zhang XJ, Chong HH, Zhu YM, Wei HM, Wu XY, He JS, Wang XQ, He YX. Enfuvirtide (T20)-Based Lipopeptide Is a Potent HIV-1 Cell Fusion Inhibitor: Implications for Viral Entry and Inhibition. J Virol. 2017;91(18):e00831-17.
21.
go back to reference Goodenow M, Huet T, Saurin W, Kwok S, Sninsky J, Wainhobson S. Hiv-1 isolates are rapidly evolving Quasispecies - evidence for viral mixtures and preferred nucleotide substitutions. J Acq Immun Def Synd. 1989;2(4):344–52. Goodenow M, Huet T, Saurin W, Kwok S, Sninsky J, Wainhobson S. Hiv-1 isolates are rapidly evolving Quasispecies - evidence for viral mixtures and preferred nucleotide substitutions. J Acq Immun Def Synd. 1989;2(4):344–52.
22.
go back to reference Smyth RP, Davenport MP, Mak J. The origin of genetic diversity in HIV-1. Virus Res. 2012;169(2):415–29.PubMedCrossRef Smyth RP, Davenport MP, Mak J. The origin of genetic diversity in HIV-1. Virus Res. 2012;169(2):415–29.PubMedCrossRef
23.
go back to reference Abrahams MR, Anderson JA, Giorgi EE, Seoighe C, Mlisana K, Ping LH, Athreya GS, Treurnicht FK, Keele BF, Wood N, et al. Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-Poisson distribution of transmitted variants (vol 83, pg 3556, 2009). J Virol. 2009;83(13):6974.PubMedCentralCrossRef Abrahams MR, Anderson JA, Giorgi EE, Seoighe C, Mlisana K, Ping LH, Athreya GS, Treurnicht FK, Keele BF, Wood N, et al. Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-Poisson distribution of transmitted variants (vol 83, pg 3556, 2009). J Virol. 2009;83(13):6974.PubMedCentralCrossRef
24.
go back to reference Li H, Bar KJ, Wang SY, Decker JM, Chen YL, Sun CX, Salazar-Gonzalez JF, Salazar MG, Learn GH, Morgan CJ et al. High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men. PLoS Pathog. 2010;6(5):e1000890. Li H, Bar KJ, Wang SY, Decker JM, Chen YL, Sun CX, Salazar-Gonzalez JF, Salazar MG, Learn GH, Morgan CJ et al. High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men. PLoS Pathog. 2010;6(5):e1000890.
25.
go back to reference Mansky LM, Temin HM. Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J Virol. 1995;69(8):5087–94.PubMedPubMedCentralCrossRef Mansky LM, Temin HM. Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J Virol. 1995;69(8):5087–94.PubMedPubMedCentralCrossRef
26.
go back to reference Jung A, Maier R, Vartanian JP, Bocharov G, Jung V, Fischer U, Meese E, Wain-Hobson S, Meyerhans A. Recombination: multiply infected spleen cells in HIV patients. Nature. 2002;418(6894):144.PubMedCrossRef Jung A, Maier R, Vartanian JP, Bocharov G, Jung V, Fischer U, Meese E, Wain-Hobson S, Meyerhans A. Recombination: multiply infected spleen cells in HIV patients. Nature. 2002;418(6894):144.PubMedCrossRef
27.
go back to reference Inoue M, Hoxie JA, Reddy MV, Srinivasan A, Reddy EP. Mechanisms associated with the generation of biologically active human immunodeficiency virus type 1 particles from defective proviruses. Proc Natl Acad Sci U S A. 1991;88(6):2278–82.PubMedPubMedCentralCrossRef Inoue M, Hoxie JA, Reddy MV, Srinivasan A, Reddy EP. Mechanisms associated with the generation of biologically active human immunodeficiency virus type 1 particles from defective proviruses. Proc Natl Acad Sci U S A. 1991;88(6):2278–82.PubMedPubMedCentralCrossRef
28.
go back to reference Piantadosi A, Chohan B, Chohan V, McClelland RS, Overbaugh J. Chronic HIV-1 infection frequently fails to protect against superinfection. PLoS Pathog. 2007;3(11):1745–60.CrossRef Piantadosi A, Chohan B, Chohan V, McClelland RS, Overbaugh J. Chronic HIV-1 infection frequently fails to protect against superinfection. PLoS Pathog. 2007;3(11):1745–60.CrossRef
29.
go back to reference Streeck H, Li B, Poon AFY, Schneidewind A, Gladden AD, Power KA, Daskalakis D, Bazner S, Zuniga R, Brander C, et al. Immune-driven recombination and loss of control after HIV superinfection. J Exp Med. 2008;205(8):1789–96.PubMedPubMedCentralCrossRef Streeck H, Li B, Poon AFY, Schneidewind A, Gladden AD, Power KA, Daskalakis D, Bazner S, Zuniga R, Brander C, et al. Immune-driven recombination and loss of control after HIV superinfection. J Exp Med. 2008;205(8):1789–96.PubMedPubMedCentralCrossRef
31.
go back to reference Simon-Loriere E, Galetto R, Hamoudi M, Archer J, Lefeuvre P, Martin DP, Robertson DL, Negroni M. Molecular mechanisms of recombination restriction in the envelope gene of the human immunodeficiency virus. PLoS Pathog. 2009;5(5):e1000418.PubMedPubMedCentralCrossRef Simon-Loriere E, Galetto R, Hamoudi M, Archer J, Lefeuvre P, Martin DP, Robertson DL, Negroni M. Molecular mechanisms of recombination restriction in the envelope gene of the human immunodeficiency virus. PLoS Pathog. 2009;5(5):e1000418.PubMedPubMedCentralCrossRef
32.
go back to reference Troyer RM, Collins KR, Abraha A, Fraundorf E, Moore DM, Krizan RW, Toossi Z, Colebunders RL, Jensen MA, Mullins JI, et al. Changes in human immunodeficiency virus type 1 fitness and genetic diversity during disease progression. J Virol. 2005;79(14):9006–18.PubMedPubMedCentralCrossRef Troyer RM, Collins KR, Abraha A, Fraundorf E, Moore DM, Krizan RW, Toossi Z, Colebunders RL, Jensen MA, Mullins JI, et al. Changes in human immunodeficiency virus type 1 fitness and genetic diversity during disease progression. J Virol. 2005;79(14):9006–18.PubMedPubMedCentralCrossRef
33.
go back to reference Njai HF, Gali Y, Vanham G, Clybergh C, Jennes W, Vidal N, Butel C, Mpoudi-Ngolle E, Peeters M, Arien KK. The predominance of human immunodeficiency virus type I (HIV-I) circulating recombinant form 02 (CRF02_AG) in west Central Africa may be related to its replicative fitness. Retrovirology. 2006;3:40. Njai HF, Gali Y, Vanham G, Clybergh C, Jennes W, Vidal N, Butel C, Mpoudi-Ngolle E, Peeters M, Arien KK. The predominance of human immunodeficiency virus type I (HIV-I) circulating recombinant form 02 (CRF02_AG) in west Central Africa may be related to its replicative fitness. Retrovirology. 2006;3:40.
34.
go back to reference Tebit DM, Nankya I, Arts EJ, Gao Y. HIV diversity, recombination and disease progression: how does fitness "fit" into the puzzle? AIDS Rev. 2007;9(2):75–87.PubMed Tebit DM, Nankya I, Arts EJ, Gao Y. HIV diversity, recombination and disease progression: how does fitness "fit" into the puzzle? AIDS Rev. 2007;9(2):75–87.PubMed
35.
go back to reference Rangel HR, Weber J, Chakraborty B, Gutierrez A, Marotta ML, Mirza M, Kiser P, Martinez MA, Este JA, Quinones-Mateu ME. Role of the human immunodeficiency virus type 1 envelope gene in viral fitness. J Virol. 2003;77(16):9069–73.PubMedPubMedCentralCrossRef Rangel HR, Weber J, Chakraborty B, Gutierrez A, Marotta ML, Mirza M, Kiser P, Martinez MA, Este JA, Quinones-Mateu ME. Role of the human immunodeficiency virus type 1 envelope gene in viral fitness. J Virol. 2003;77(16):9069–73.PubMedPubMedCentralCrossRef
36.
go back to reference Fourati S, Lambert-Niclot S, Soulie C, Malet I, Valantin MA, Descours B, Ait-Arkoub Z, Mory B, Carcelain G, Katlama C, et al. HIV-1 genome is often defective in PBMCs and rectal tissues after long-term HAART as a result of APOBEC3 editing and correlates with the size of reservoirs. J Antimicrob Chemoth. 2012;67(10):2323–6.CrossRef Fourati S, Lambert-Niclot S, Soulie C, Malet I, Valantin MA, Descours B, Ait-Arkoub Z, Mory B, Carcelain G, Katlama C, et al. HIV-1 genome is often defective in PBMCs and rectal tissues after long-term HAART as a result of APOBEC3 editing and correlates with the size of reservoirs. J Antimicrob Chemoth. 2012;67(10):2323–6.CrossRef
37.
go back to reference Arenaccio C, Anticoli S, Manfredi F, Chiozzini C, Olivetta E, Federico M. Latent HIV-1 is activated by exosomes from cells infected with either replication-competent or defective HIV-1. Retrovirology. 2015;12:87. Arenaccio C, Anticoli S, Manfredi F, Chiozzini C, Olivetta E, Federico M. Latent HIV-1 is activated by exosomes from cells infected with either replication-competent or defective HIV-1. Retrovirology. 2015;12:87.
38.
go back to reference Liao HK, Gu Y, Diaz A, Marlett J, Takahashi Y, Li M, Suzuki K, Xu R, Hishida T, Chang CJ, et al. Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells. Nat Commun. 2015;6. Liao HK, Gu Y, Diaz A, Marlett J, Takahashi Y, Li M, Suzuki K, Xu R, Hishida T, Chang CJ, et al. Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells. Nat Commun. 2015;6.
39.
go back to reference Zhu WJ, Lei RY, Le Duff Y, Li J, Guo F, Wainberg MA, Liang C. The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Retrovirology. 2015;12. Zhu WJ, Lei RY, Le Duff Y, Li J, Guo F, Wainberg MA, Liang C. The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Retrovirology. 2015;12.
40.
go back to reference Pegu A, Asokan M, Wu L, Wang KY, Hataye J, Casazza JP, Guo XT, Shi W, Georgiev I, Zhou TQ, et al. Activation and lysis of human CD4 cells latently infected with HIV-1. Nat Commun. 2015;6. Pegu A, Asokan M, Wu L, Wang KY, Hataye J, Casazza JP, Guo XT, Shi W, Georgiev I, Zhou TQ, et al. Activation and lysis of human CD4 cells latently infected with HIV-1. Nat Commun. 2015;6.
Metadata
Title
Defective HIV-1 envelope gene promotes the evolution of the infectious strain through recombination in vitro
Authors
Huamian Wei
Danwei Yu
Xiuzhu Geng
Yuxian He
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2020
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-020-05288-w

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