Evolution of the HIV-1 Envelope Glycoproteins with a Disulfide Bond Between Gp120 and Gp41

Overview

Journal Retrovirology

Publisher Biomed Central

Specialty Microbiology

Date 2004 Jun 1

PMID 15169554

Citations 16

Authors

Rogier W Sanders

Martijn M Dankers

Els Busser

Michael Caffrey

John P Moore

Ben Berkhout

Affiliations

Soon will be listed here.

Abstract

Background: We previously described the construction of an HIV-1 envelope glycoprotein complex (Env) that is stabilized by an engineered intermolecular disulfide bond (SOS) between gp120 and gp41. The modified Env protein antigenically mimics the functional wild-type Env complex. Here, we explore the effects of the covalent gp120 - gp41 interaction on virus replication and evolution.

Results: An HIV-1 molecular clone containing the SOS Env gene was only minimally replication competent, suggesting that the engineered disulfide bond substantially impaired Env function. However, virus evolution occurred in cell culture infections, and it eventually always led to elimination of the intermolecular disulfide bond. In the course of these evolution studies, we identified additional and unusual second-site reversions within gp41.

Conclusions: These evolution paths highlight residues that play an important role in the interaction between gp120 and gp41. Furthermore, our results suggest that a covalent gp120 - gp41 interaction is incompatible with HIV-1 Env function, probably because this impedes conformational changes that are necessary for fusion to occur, which may involve the complete dissociation of gp120 from gp41.

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References

Caffrey M, Cai M, Kaufman J, Stahl S, Wingfield P, Covell D . Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41. EMBO J. 1998; 17(16):4572-84. PMC: 1170787. DOI: 10.1093/emboj/17.16.4572. View

McKeating J, McKnight A, Moore J . Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: effects on infectivity and neutralization. J Virol. 1991; 65(2):852-60. PMC: 239825. DOI: 10.1128/JVI.65.2.852-860.1991. View

Sakurai H, Williamson R, Crowe J, Beeler J, Poignard P, Bastidas R . Human antibody responses to mature and immature forms of viral envelope in respiratory syncytial virus infection: significance for subunit vaccines. J Virol. 1999; 73(4):2956-62. PMC: 104055. DOI: 10.1128/JVI.73.4.2956-2962.1999. View

Yang Z, Mueser T, Kaufman J, Stahl S, Wingfield P, Hyde C . The crystal structure of the SIV gp41 ectodomain at 1.47 A resolution. J Struct Biol. 1999; 126(2):131-44. DOI: 10.1006/jsbi.1999.4116. View

Parren P, Burton D, Sattentau Q . HIV-1 antibody--debris or virion?. Nat Med. 1997; 3(4):366-7. DOI: 10.1038/nm0497-366d. View

Chan D, Fass D, Berger J, Kim P . Core structure of gp41 from the HIV envelope glycoprotein. Cell. 1997; 89(2):263-73. DOI: 10.1016/s0092-8674(00)80205-6. View

Peden K, Emerman M, Montagnier L . Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI. Virology. 1991; 185(2):661-72. DOI: 10.1016/0042-6822(91)90537-l. View

Lopalco L, Longhi R, Ciccomascolo F, De Rossi A, Pelagi M, Andronico F . Identification of human immunodeficiency virus type 1 glycoprotein gp120/gp41 interacting sites by the idiotypic mimicry of two monoclonal antibodies. AIDS Res Hum Retroviruses. 1993; 9(1):33-9. DOI: 10.1089/aid.1993.9.33. View

Cao J, Bergeron L, Helseth E, Thali M, Repke H, Sodroski J . Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein. J Virol. 1993; 67(5):2747-55. PMC: 237598. DOI: 10.1128/JVI.67.5.2747-2755.1993. View

10.

Chen S . Functional role of the zipper motif region of human immunodeficiency virus type 1 transmembrane protein gp41. J Virol. 1994; 68(3):2002-10. PMC: 236667. DOI: 10.1128/JVI.68.3.2002-2010.1994. View

11.

Das A, Klaver B, Klasens B, van Wamel J, Berkhout B . A conserved hairpin motif in the R-U5 region of the human immunodeficiency virus type 1 RNA genome is essential for replication. J Virol. 1997; 71(3):2346-56. PMC: 191344. DOI: 10.1128/JVI.71.3.2346-2356.1997. View

12.

Weissenhorn W, Dessen A, Harrison S, Skehel J, Wiley D . Atomic structure of the ectodomain from HIV-1 gp41. Nature. 1997; 387(6631):426-30. DOI: 10.1038/387426a0. View

13.

Parren P, Gauduin M, Koup R, Poignard P, Fisicaro P, Burton D . Relevance of the antibody response against human immunodeficiency virus type 1 envelope to vaccine design. Immunol Lett. 1997; 57(1-3):105-12. DOI: 10.1016/s0165-2478(97)00043-6. View

14.

Tan K, Liu J, Wang J, Shen S, Lu M . Atomic structure of a thermostable subdomain of HIV-1 gp41. Proc Natl Acad Sci U S A. 1997; 94(23):12303-8. PMC: 24915. DOI: 10.1073/pnas.94.23.12303. View

15.

Wyatt R, Sodroski J . The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science. 1998; 280(5371):1884-8. DOI: 10.1126/science.280.5371.1884. View

16.

Opstelten D, Wallin M, Garoff H . Moloney murine leukemia virus envelope protein subunits, gp70 and Pr15E, form a stable disulfide-linked complex. J Virol. 1998; 72(8):6537-45. PMC: 109824. DOI: 10.1128/JVI.72.8.6537-6545.1998. View

17.

Binley J, Sanders R, CLAS B, Schuelke N, Master A, Guo Y . A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J Virol. 2000; 74(2):627-43. PMC: 111582. DOI: 10.1128/jvi.74.2.627-643.2000. View

18.

Jeeninga R, Hoogenkamp M, de Baar M, Verhoef K, Berkhout B . Functional differences between the long terminal repeat transcriptional promoters of human immunodeficiency virus type 1 subtypes A through G. J Virol. 2000; 74(8):3740-51. PMC: 111883. DOI: 10.1128/jvi.74.8.3740-3751.2000. View

19.

Sanders R, Schiffner L, Master A, Kajumo F, Guo Y, Dragic T . Variable-loop-deleted variants of the human immunodeficiency virus type 1 envelope glycoprotein can be stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits. J Virol. 2000; 74(11):5091-100. PMC: 110861. DOI: 10.1128/jvi.74.11.5091-5100.2000. View

20.

Parren P, Moore J, Burton D, Sattentau Q . The neutralizing antibody response to HIV-1: viral evasion and escape from humoral immunity. AIDS. 2000; 13 Suppl A:S137-62. View