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Related Concept Videos

Rab Cascades01:25

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
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Rabies

Rabies is a lethal zoonotic disease caused by a single-stranded, negative-sense RNA virus of the Lyssavirus genus, within the family Rhabdoviridae. Its primary mode of transmission to humans is through bites or saliva-contaminated scratches from infected mammals such as dogs, bats, raccoons, or foxes. Transmission can also occur if infectious saliva contacts abraded skin or intact mucous membranes, including the conjunctiva.Viral Entry and Early ReplicationOnce introduced at the bite or scratch...

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Two Methods of Heterokaryon Formation to Discover HCV Restriction Factors
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BCA2/Rabring7 promotes tetherin-dependent HIV-1 restriction.

Kei Miyakawa1, Akihide Ryo, Tsutomu Murakami

  • 1AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.

Plos Pathogens
|December 19, 2009
PubMed
Summary

Breast cancer-associated gene 2 (BCA2) is a host protein that works with tetherin to restrict HIV-1 release. BCA2 promotes the internalization and degradation of viral particles after tethering, enhancing HIV-1 restriction.

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Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Host cell factors regulate Human Immunodeficiency Virus type 1 (HIV-1) assembly and egress.
  • Tetherin (CD317/BST-2) is a host restriction factor inhibiting HIV-1 particle release by retaining virions on the cell surface.
  • The molecular mechanisms of tetherin-mediated HIV-1 restriction are not fully understood.

Purpose of the Study:

  • Identify novel host proteins interacting with tetherin.
  • Investigate the role of Breast cancer-associated gene 2 (BCA2) in HIV-1 restriction.
  • Elucidate the mechanism by which BCA2 influences HIV-1 particle release.

Main Methods:

  • Co-expression of BCA2 and tetherin in cell lines (HeLa, HOS).
  • RNA interference (RNAi) to deplete endogenous BCA2.
  • Analysis of HIV-1 particle production and intracellular accumulation.
  • Tracking of virion internalization and degradation via CD63(+) vesicles.

Main Results:

  • BCA2 restricts HIV-1 particle production in tetherin-positive cells.
  • BCA2 facilitates the internalization of HIV-1 virions into CD63(+) intracellular vesicles.
  • Depletion of BCA2 reduces intracellular viral particle accumulation but virions remain cell-surface tethered.
  • BCA2 enhances tetherin-dependent restriction of HIV-1 release.

Conclusions:

  • BCA2 is a novel tetherin-interacting host protein.
  • BCA2 accelerates the internalization and lysosomal degradation of tethered HIV-1 virions.
  • BCA2 acts as a co-factor or enhancer for tetherin in restricting HIV-1 release.