Human Immunodeficiency Virus (HIV) Envelope Binds to CXCR4 Independently of CD4, and Binding Can Be Enhanced by Interaction with Soluble CD4 or by HIV Envelope Deglycosylation

Bandrés, Juan C.; Wang, Qing F.; O’Leary, Jeanne; Baleaux, Françoise; Amara, Ali; Hoxie, James A.; Zolla‐Pazner, Susan; Górny, Miroslaw K.

doi:10.1128/jvi.72.3.2500-2504.1998

Cited by 90 publications

(30 citation statements)

References 32 publications

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“…Several other studies demonstrated that prebinding soluble forms of Tva to ALV(A) virions produced activated viruses capable of infecting Tva-negative cells (10,17,60). Viral envelope preactivation has also been proposed for the observed enhancement of infection of CD4-negative cells by some HIV and simian immunodeficiency virus variants preadsorbed with soluble CD4 (6,57). A variety of selective forces, including development of resistance to viral entry by the host, are probably responsible for retroviruses evolving to use different receptors.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Residues in Subgroup A Avian Leukosis Virus Envelope Determining Receptor Binding Affinity and Infectivity of Cells Expressing Chicken or Quail Tva Receptor

Holmen

Melder

Federspiel

2001

J Virol

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Section: Discussionmentioning

confidence: 99%

Identification of Key Residues in Subgroup A Avian Leukosis Virus Envelope Determining Receptor Binding Affinity and Infectivity of Cells Expressing Chicken or Quail Tva Receptor

Holmen

Melder

Federspiel

2001

J Virol

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“…These include proteolytic processing, protein folding, and glycosylation. Glycosylation of the hemagglutinin of influenza A and envelope of lentiviruses can have dramatic effects on cleavage activation, immune escape, virulence, and interactions with cellular receptors (3,6,7,12,13,16,27,47,53,55,56,76). In contrast to the ample information regarding effects of glycosylation on virus attachment proteins is the limited knowledge of the effects of receptor glycosylation on virus-receptor interactions.…”

Section: Discussionmentioning

confidence: 99%

Molecular Determinants of Species Specificity in the Coronavirus Receptor Aminopeptidase N (CD13): Influence of N-Linked Glycosylation

Wentworth

Holmes

2001

J Virol

106

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Aminopeptidase N (APN), a 150-kDa metalloprotease also called CD13, serves as a receptor for serologically related coronaviruses of humans (human coronavirus 229E [HCoV-229E]), pigs, and cats. These virusreceptor interactions can be highly species specific; for example, the human coronavirus can use human APN (hAPN) but not porcine APN (pAPN) as its cellular receptor, and porcine coronaviruses can use pAPN but not hAPN. Substitution of pAPN amino acids 283 to 290 into hAPN for the corresponding amino acids 288 to 295 introduced an N-glycosylation sequon at amino acids 291 to 293 that blocked HCoV-229E receptor activity of hAPN. Substitution of two amino acids that inserted an N-glycosylation site at amino acid 291 also resulted in a mutant hAPN that lacked receptor activity because it failed to bind HCoV-229E. Single amino acid revertants that removed this sequon at amino acids 291 to 293 but had one or five pAPN amino acid substitution(s) in this region all regained HCoV-229E binding and receptor activities. To determine if other N-linked glycosylation differences between hAPN, feline APN (fAPN), and pAPN account for receptor specificity of pig and cat coronaviruses, a mutant hAPN protein that, like fAPN and pAPN, lacked a glycosylation sequon at 818 to 820 was studied. This sequon is within the region that determines receptor activity for porcine and feline coronaviruses. Mutant hAPN lacking the sequon at amino acids 818 to 820 maintained HCoV-229E receptor activity but did not gain receptor activity for porcine or feline coronaviruses. Thus, certain differences in glycosylation between coronavirus receptors from different species are critical determinants in the species specificity of infection.Human coronaviruses (HCoV) in two serogroups represented by HCoV-229E (serogroup 1) and HCoV-OC43 (serogroup 2) are an important cause of upper respiratory tract infection. Serological studies suggest that they cause from 15 to 30% of human upper respiratory infections or colds (25). Although there is no animal model for the pathogenesis of HCoV respiratory infections, HCoV-229E and HCoV-OC43 have been administered intranasally to human volunteers, and this has shown that people can be repeatedly infected by the same strain (5). There is also in vitro and in vivo evidence for infection of cells of the central nervous system (CNS) by HCoV (39,51,68,69). Coronaviruses have a lipid membrane that has large peplomers that protrude from the virion and give it the appearance of a corona. These peplomers or spike glycoproteins are the viral attachment proteins. The 27-kb genomic RNA of HCoV-229E is positive sense, has a 5Ј cap, is polyadenylated at the 3Ј terminus, and is infectious when transfected into cells of a wide variety of species (25). In contrast, infection by HCoV-229E virions is limited to cells of human or feline origin in vitro, demonstrating that the receptor for HCoV-229E is a major determinant in species specificity (25).The cellular receptor for HCoV-229E is human aminopeptidase N (hAPN). HCoV-229E infection ...

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“…The identification of small-molecule antagonists of CXCR4 and readily selected strains of HIV-1 that can resist inhibitor challenges highlights the flexibility of Env and the need to understand the interaction of ligands with CXCR4 to design more effective antiretroviral agents (20,21,38,46,49,56). Recent advances in detecting direct Env interactions with CCR5 have enhanced our understanding of the role of the chemokine receptors in fusion (37,41,52,61,67,68), but direct interactions of X4 Envs with CXCR4 have been difficult to study (4,34,39,43).…”

mentioning

confidence: 99%

Identification of CXCR4 Domains That Support Coreceptor and Chemokine Receptor Functions

Doranz

Orsini

Turner

et al. 1999

J Virol

Self Cite

207

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The interaction of the chemokine stromal cell-derived factor 1 (SDF-1) with its receptor CXCR4 is vital for cell trafficking during development, is capable of inhibiting human immunodeficiency virus type 1 (HIV-1) utilization of CXCR4 as a coreceptor, and has been implicated in delaying disease progression to AIDS in vivo. Because of the importance of this chemokine-chemokine receptor pair to both development and disease, we investigated the molecular basis of the interaction between CXCR4 and its ligands SDF-1 and HIV-1 envelope. Using CXCR4 chimeras and mutants, we determined that SDF-1 requires the CXCR4 amino terminus for binding and activates downstream signaling pathways by interacting with the second extracellular loop of CXCR4. SDF-1-mediated activation of CXCR4 required the Asp-Arg-Tyr motif in the second intracellular loop of CXCR4, was pertussis toxin sensitive, and did not require the distal C-terminal tail of CXCR4. Several CXCR4 mutants that were not capable of binding SDF-1 or signaling still supported HIV-1 infection, indicating that the ability of CXCR4 to function as a coreceptor is independent of its ability to signal. Direct binding studies using the X4 gp120s HXB, BH8, and MN demonstrated the ability of HIV-1 gp120 to bind directly and specifically to the chemokine receptor CXCR4 in a CD4-dependent manner, using a conformationally complex structure on CXCR4. Several CXCR4 variants that did not support binding of soluble gp120 could still function as viral coreceptors, indicating that detectable binding of monomeric gp120 is not always predictive of coreceptor function.

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Human Immunodeficiency Virus (HIV) Envelope Binds to CXCR4 Independently of CD4, and Binding Can Be Enhanced by Interaction with Soluble CD4 or by HIV Envelope Deglycosylation

Cited by 90 publications

References 32 publications

Identification of Key Residues in Subgroup A Avian Leukosis Virus Envelope Determining Receptor Binding Affinity and Infectivity of Cells Expressing Chicken or Quail Tva Receptor

Identification of Key Residues in Subgroup A Avian Leukosis Virus Envelope Determining Receptor Binding Affinity and Infectivity of Cells Expressing Chicken or Quail Tva Receptor

Molecular Determinants of Species Specificity in the Coronavirus Receptor Aminopeptidase N (CD13): Influence of N-Linked Glycosylation

Identification of CXCR4 Domains That Support Coreceptor and Chemokine Receptor Functions

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