Identification of four antibody-binding sites in the envelope proteins of simian immunodeficiency virus, SIVsm

AIDS ◽  
1993 ◽  
Vol 7 (2) ◽  
pp. 159-166 ◽  
Author(s):  
Astrid Samuelsson ◽  
Ewa Björling ◽  
Per Putkonen ◽  
Göran Utter ◽  
Francesca Chiodi ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Binding Sites ◽  
Envelope Proteins ◽  
Antibody Binding ◽  
Immunodeficiency Virus

scholarly journals Kinetic Rates of Antibody Binding Correlate with Neutralization Sensitivity of Variant Simian Immunodeficiency Virus Strains

2005 ◽  
Vol 79 (19) ◽  
pp. 12311-12320 ◽  
Author(s):  
Jonathan D. Steckbeck ◽  
Irina Orlov ◽  
Andrew Chow ◽  
Heather Grieser ◽  
Kenneth Miller ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Simian Immunodeficiency Virus ◽  
Neutralizing Antibody ◽  
Envelope Proteins ◽  
Antibody Binding ◽  
Immunodeficiency Virus ◽  
Kinetic Rates ◽  
Aids Vaccines ◽  
Virus Strains

ABSTRACT Increasing evidence suggests that an effective AIDS vaccine will need to elicit both broadly reactive humoral and cellular immune responses. Potent and cross-reactive neutralization of simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) by polyclonal and monoclonal antibodies is well documented. However, the mechanisms of antibody-mediated neutralization have not been defined. The current study was designed to determine whether the specificity and quantitative properties of antibody binding to SIV envelope proteins correlate with neutralization. Using a panel of rhesus monoclonal antibodies previously characterized for their ability to bind and neutralize variant SIVs, we compared the kinetic rates and affinity of antibody binding to soluble envelope trimers by using surface plasmon resonance. We identified significant differences in the kinetic rates but not the affinity of monoclonal antibody binding to the neutralization-sensitive SIV/17E-CL and neutralization-resistant SIVmac239 envelope proteins that correlated with the neutralization sensitivities of the corresponding virus strains. These results suggest for the first time that neutralization resistance may be related to quantitative differences in the rates but not the affinity of the antibody-envelope interaction and may provide one mechanism for the inherent resistance of SIVmac239 to neutralization in vitro. Further, we provide evidence that factors in addition to antibody binding, such as epitope specificity, contribute to the mechanisms of neutralization of SIV/17E-CL in vitro. This study will impact the method by which HIV/SIV vaccines are evaluated and will influence the design of candidate AIDS vaccines capable of eliciting effective neutralizing antibody responses.

scholarly journals Effect of the Cytoplasmic Domain of the Simian Immunodeficiency Virus Envelope Protein on Incorporation of Heterologous Envelope Proteins and Sensitivity to Neutralization

2000 ◽  
Vol 74 (18) ◽  
pp. 8219-8225 ◽  
Author(s):  
A. N. Vzorov ◽  
R. W. Compans
Keyword(s):  
Influenza Virus ◽  
Host Cell ◽  
Simian Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Cytoplasmic Domain ◽  
Envelope Proteins ◽  
Viral Envelope ◽  
Full Length ◽  
Viral Glycoprotein ◽  
Immunodeficiency Virus

ABSTRACT In addition to the viral envelope (Env) proteins, host cell-derived proteins have been reported to be present in human immunodeficiency virus and simian immunodeficiency virus (SIV) envelopes, and it has been postulated that they may play a role in infection. We investigated whether the incorporation of host cell proteins is affected by the structure and level of incorporation of viral Env proteins. To compare the cellular components incorporated into SIV particles and how this is influenced by the structure of the cytoplasmic domain, we compared SIV virions with full-length and truncated Env proteins. The levels of HLA-I and HLA-II molecules were found to be significantly (15- to 25-fold) higher in virions with full-length Env than in those with a truncated Env. Virions with a truncated Env were also found to be less susceptible to neutralization by specific antibodies against HLA-I or HLA-II proteins. We also compared the level of incorporation into SIV virions of a coexpressed heterologous viral glycoprotein, the influenza virus hemagglutinin (HA) protein. We found that SIV infection of cells expressing influenza virus HA resulted in the production of phenotypically mixed SIV virions containing influenza virus HA as well as SIV envelope proteins. The HA proteins were more effectively incorporated into virions with full-length Env than in virions with truncated Env. The phenotypically mixed particles with full-length Env, containing higher levels of HA, were sensitive to neutralization with anti-HA antibody, whereas virions with truncated Env proteins and containing lower levels of HA were more resistant to neutralization by anti-HA antibody. In contrast, SIV virions with truncated Env proteins were found to be highly sensitive to neutralization by antisera to SIV, whereas virions with full-length Env proteins were relatively resistant to neutralization. These results indicate that the cytoplasmic domain of SIV Env affects the incorporation of cellular as well as heterologous viral membrane proteins into the SIV envelope and may be an important determinant of the sensitivity of the virus to neutralizing antibodies.

scholarly journals Sequences Just Upstream of the Simian Immunodeficiency Virus Core Enhancer Allow Efficient Replication in the Absence of NF-κB and Sp1 Binding Elements

1998 ◽  
Vol 72 (7) ◽  
pp. 5589-5598 ◽  
Author(s):  
Stefan Pöhlmann ◽  
Stefan Flöss ◽  
Petr O. Ilyinskii ◽  
Thomas Stamminger ◽  
Frank Kirchhoff
Keyword(s):  
Viral Replication ◽  
Binding Site ◽  
Simian Immunodeficiency Virus ◽  
Binding Sites ◽  
Regulatory Element ◽  
Virus Production ◽  
Enhancer Element ◽  
Immunodeficiency Virus ◽  
Efficient Replication

ABSTRACT Large deletions of the upstream U3 sequences in the long terminal repeats (LTRs) of human immunodeficiency virus and simian immunodeficiency virus (SIV) accumulate in vivo in the absence of an intact nef gene. In the SIV U3 region, about 65 bp just upstream of the single NF-κB binding site always remained intact, and some evidence for a novel enhancer element in this region exists. We analyzed the transcriptional and replicative capacities of SIVmac239 mutants containing deletions or mutations in these upstream U3 sequences and/or the NF-κB and Sp1 binding sites. Even in the absence of 400 bp of upstream U3 sequences, the NF-κB site and all four Sp1 binding sites, the SIV promoter maintained about 15% of the wild-type LTR activity and was fully responsive to Tat activation in transient reporter assays. The effects of these deletions on virus production after transfection of COS-1 cells with full-length proviral constructs were much greater. Deletion of the upstream U3 sequences had no significant influence on viral replication when either the single NF-κB site or the Sp1 binding sites were intact. In contrast, the 26 bp of sequence located immediately upstream of the NF-κB site was essential for efficient replication when all core enhancer elements were deleted. A purine-rich site in this region binds specifically to the transcription factor Elf-1, a member of the etsproto-oncogene-encoded family. Our results indicate a high degree of functional redundancy in the SIVmac U3 region. Furthermore, we defined a novel regulatory element located immediately upstream of the NF-κB binding site that allows efficient viral replication in the absence of the entire core enhancer region.

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