Coreceptor-dependent inhibition of the cell fusion activity of simian immunodeficiency virus Env proteins

C Yang1, Q Yang, R W Compans

  • 1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Journal of Virology
|June 14, 2000
PubMed

Insights

The R peptide sequence inhibits fusion for simian immunodeficiency virus (SIV)-murine leukemia virus (MuLV) chimeric envelope proteins. However, this inhibition is reduced when cells express the CCR5 coreceptor, indicating differential effects based on coreceptor type.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • The cytoplasmic tail (R peptide) of the murine leukemia virus (MuLV) envelope (Env) protein regulates fusion activity.
  • Simian immunodeficiency virus (SIV) utilizes various cellular coreceptors for cell entry.
  • Previous studies indicated the R peptide inhibits fusion in SIV-MuLV chimeric Env proteins.

Purpose of the Study:

  • To investigate the fusion activity of SIV and SIV-MuLV chimeric Env proteins.
  • To determine the effect of different cellular coreceptors on R peptide-mediated fusion regulation.
  • To understand the differential impact of the R peptide on SIV Env fusion using alternative coreceptors.

Main Methods:

  • Transfection of HeLa cells with SIV or SIV-MuLV chimeric Env protein genes.
  • Cocultivation of transfected HeLa cells with target cells expressing specific SIV coreceptors (Gpr15 or CCR5).
  • Assessment of viral fusion activity based on Env protein expression and coreceptor presence.

Main Results:

  • The R peptide sequence inhibited fusion with CEMx174 cells and Ghost Gpr15 cells (Gpr15 coreceptor).
  • A significant level of fusion was observed when using Ghost CCR5 cells (CCR5 coreceptor).
  • The R peptide's inhibitory effect on SIV Env fusion varied depending on the target cell's coreceptor.

Conclusions:

  • The R peptide sequence exhibits differential regulation of SIV Env fusion activity.
  • Coreceptor usage significantly influences the inhibitory effect of the R peptide.
  • These findings highlight the complex interplay between viral Env proteins, coreceptors, and fusion regulation in SIV entry.

Related Concept Videos

Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
SNAREs and Membrane Fusion01:43

SNAREs and Membrane Fusion

Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...