Mutation of conserved N-glycosylation sites around the CD4-binding site of human immunodeficiency virus type 1 GP120 affects viral infectivity

Dirckx, Luc; Lindemann, Dirk; Ette, R.; Manzoni, Carlo; Moritz, Dirk; Mous, Jan

doi:10.1016/0168-1702(90)90085-p

Cited by 26 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The glycosylation of envelope protein is essential for the proper folding of receptor binding sites in human immunodeficiency virus [22,23]. In addition, in Friend MLV, secretion of Env-SU was prevented when N-linked oligosaccharide was eliminated [24].…”

Section: Discussionmentioning

confidence: 99%

Cell-binding properties of the envelope proteins of porcine endogenous retroviruses

Watanabe

Miyazawa

Matsuura

2005

Microbes and Infection

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Cell-binding properties of the envelope proteins of porcine endogenous retroviruses

Watanabe

Miyazawa

Matsuura

2005

Microbes and Infection

View full text Add to dashboard Cite

“…Further, the NXS and NXT sequon regions are clearly distinguishable. It may be noticed that on or near the protein interaction regions (marked by green arrow-heads), for example, at amino acid position 425-430 (CD4 binding site) 7, 15, the sequon probability is virtually zero. Further, parts of the variable loops (V 1 /V 2 and V 3 ) do not contain any N-glycosylation sites (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…For example, inhibition studies have demonstrated that proper N-glycosylation of gp120 is critical for the infectivity of the virus 14. Mutation studies have indicated that N-glycosylation around the CD4 binding site of the gp120 is required for high affinity receptor interaction 10, 15. It has been suggested that the HIV uses this 'glycan shield' on gp120 for the purpose of host immune evasion 16.…”

Section: Introductionmentioning

confidence: 99%

Subtle evolutionary changes in the distribution of N-glycosylation sequons in the HIV-1 envelope glycoprotein 120

Rao¹,

Wollenweber²

2010

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Many viruses are known to undergo rapid evolutionary changes under selective pressures. The HIV-1 envelope glycoprotein 120 (gp120) shows extreme selection for NXS/T sequons, the potential sites of N-glycosylation. Although the average number of sequons in gp120 appears to be relatively stable in the recent past, even slight changes in the distribution of sequons may potentially play crucial roles in protein interaction and viral infection. This study tracked the prevalence and distribution of NXS/T sequons in gp120 over a period of 29 years (from 1981 to 2009). The gp120 showed location specific distribution of sequons with higher density in the outer domain of the molecule. The NXT sequon density decreased in the outer domain (despite the increase in the sequon specific amino acid threonine), but increased in the inner domain. By contrast, the NXS sequon density increased specifically in the outer domain. Related changes were also seen in the distribution probabilities of sequons in two domains. The results indicate that the gp120, chiefly in subtype B, is redistributing NXS/T sequons within the molecule with specific selection for NXS sequons. The subtle evolution of sequons in gp120 may have implications in viral resistance and infection.

show abstract

“…The present data show that not even increasing the cellular concentration of mutated e n v gene products by 20-fold, could restore the biological defect associated with elimination of Cys 418. Dirckx et al [5] reported that elimination of three sites for N-linked glycosylation in the same region resulted in a significant reduction in the CD4-binding ability of gp 120. The discrepancy between their results and the ones of the present paper may be explained by the fact that these authors used a baculovirus expression system.…”

Section: Fusion Activity Of Mutated Env Gene Productsmentioning

confidence: 98%

Identification of three N-linked glycans in the V4–V5 region of HIV-1 gp 120, dispensable for CD4-binding and fusion activity of gp 120

Hemming

Bolmstedt

Jansson

et al. 1994

Archives of Virology

View full text Add to dashboard Cite

Site-directed mutagenesis was used to study the biological significance of three N-linked glycans (linked to Asn406, Asn448, and Asn463), situated in the CD4-binding region of gp120. Mutagenesis was carried out in a phage M13 system, and the mutated env genes were inserted into recombinant vaccinia virus (r-vaccinia virus). To evaluate if the level of expression affected the biological phenotype of mutant gp120, we expressed the envelope glycoproteins using either a weak (7.5 K) or a strong (11 K) promoter of vaccinia virus. The expression of mutated env proteins was analyzed after infecting CD4-expressing HeLa cells with the r-vaccinia virus, by monitoring the ability of the infected cells to generate CD4-dependent syncytia. Env gene products lacking all three glycans as well as env gene products lacking different permutations of one or two glycans were analyzed. All mutated gp120 species had the expected electrophoretical mobility as anticipated from elimination of one, two, and three N-linked glycans, respectively. Moreover, all mutant env gene products demonstrated the same capacity to induce formation of syncytia, irrespective of using the weak or strong promoter for expression. These data indicate that the three N-linked glycans studied are dispensable for HIV env gene products to function in CD4-binding and the subsequent fusion step.

show abstract

Mutation of conserved N-glycosylation sites around the CD4-binding site of human immunodeficiency virus type 1 GP120 affects viral infectivity

Cited by 26 publications

References 32 publications

Cell-binding properties of the envelope proteins of porcine endogenous retroviruses

Cell-binding properties of the envelope proteins of porcine endogenous retroviruses

Subtle evolutionary changes in the distribution of N-glycosylation sequons in the HIV-1 envelope glycoprotein 120

Identification of three N-linked glycans in the V4–V5 region of HIV-1 gp 120, dispensable for CD4-binding and fusion activity of gp 120

Contact Info

Product

Resources

About