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Casey Finnerty

Correlation Between Infectivity and Physical Virus Particles in Human Cytomegalovirus - 0 views

jb.asm.org/...1555.short

shared by Casey Finnerty on 07 Nov 14 - No Cached
  • Unlike the high particle-infectivity ratio of 106 to 108 previously reported for these viruses, the number of total particles per PFU ranged from 160 to 490 with strain AD-169 and from 176 to 1,050 for strain C-87.
Sean Hogan

Rabies Virus Hijacks and Accelerates the p75NTR Retrograde Axonal Transport Machinery - 14 views

www.ncbi.nlm.nih.gov/...PMC4148448

shared by Sean Hogan on 03 Nov 14 - No Cached
  • Our data support this finding, as we demonstrated that RABV is transported in acidic compartments (Fig. 6), and mostly in p75NTR-positive endosomes (Fig. 7).
    • nleonard11
      nleonard11 on 05 Nov 14
       
      Why is RABV transported in acidic compartments? 
  • RABV enters the peripheral nervous system and undergoes long-distance transport arriving at the cell soma and subsequently the CNS [6]. As peripheral neurons are highly polarized cells with long axons, active intracellular transport is vital to the maintenance of neuronal function and survival [7], [8]
    • laceemarie
      laceemarie on 07 Nov 14
       
      As RABV is travelling along the axons, does it interfere with the nerve signals that are also travelling there? I know that rabies results in quite a few neurological symptoms, but do these occur when the virus reaches the central nervous system (ultimately the brain) or as soon as RABV enters an axon of the PNS?
  • In neurons, infected cells may mistake RABV particles for cargo and thus recruit trafficking components, allowing viral particles to undergo long-range axonal transport to the neuronal cell body, as was found in the case of adenovirus and the CAR receptor
    • ameliaobert
      ameliaobert on 07 Nov 14
       
      Most confusing: How would a cell "mistake" a virus particle for cargo and then give it direct access to the nucleus? Does it have specific signals radiating from it or receptors that triggers this trafficking component mishap?
  • ...6 more annotations...
  • we suggest that RABV hijacks a specific mechanism that enables the neuron to transport cargos over long distances.
    • ameliaobert
      ameliaobert on 07 Nov 14
       
      To my further question: is this the cellular "mistake" that is happening by the cell that aids in trafficking of this virus? If so interesting that is isn't the cell itself, but the virus taking over a cellular process.
  • Rabies virus (RABV) is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system (CNS).
    • alexridesducati
      alexridesducati on 07 Nov 14
       
      This research shows that RABV doesnt need to be transported via p75NTR, but when it is, it is done with acidic compartments and reaches the target area faster. Also, it was mentioned that the acididty of the compartment induced a conformational change of the virus for membrane fusion. Is there any sort of correlation between speed and compartment acidity, or are there significant structural changes due to acidity that may allow for the virus to reach its destination sooner than if it were p75NTR independent?
  • Measuring both the area and average intensities of the RABV particles in each group, we found that the p75NTR positive RABV particles were larger in size, (average area of 1.34±0.09 µm2 vs. 0.81±0.07 µm2, p<0.0005), and had stronger intensity of GFP signal, when normalized to the average intensity of RABV particles in each experiment (1.24±0.11 vs. 0.61±0.1, p<0.001) (Fig. 8K–L).
    • abachman12
      abachman12 on 07 Nov 14
       
      Does this occur naturally within the human body? So does this mean that the rabies virus can be even more dangerous than it already is?
  • ence there are likely to be additional ways for RABV to merge into the p75NTR-RABV endosome
    • rmeloche10
      rmeloche10 on 07 Nov 14
       
      Is there any sort of idea on the other ways that RABV can merge into an endosome, or is this just theoretical?
  • Other membrane-associated components have also been implicated in RABV binding [20]. By binding one of its receptors, RABV could enter the cell and activate downstream signaling which would allow it to hijack and manipulate axonal transport machineries. Although p75NTR is known to be involved in the retrograde transport of neurotrophic factors, little is known regarding its direct contribution to viral transport.
    • Sean Hogan
      Sean Hogan on 07 Nov 14
       
      Is the p75NTR receptor internalized and does it become part of the endosomal membrane during RABV internalization? Could continued signaling from the receptor bound to the endosome membrane be responsible for the manipulation of the axonal transport?
  • Possibly, RABV binding to dynein tethers projecting microtubules (MT) in the cell cortex thereby facilitating its retrograde trafficking from the cell periphery. Following this tethering, RABV particles can merge into the RABV-p75NTR endosomes and travel to the neuron cell body.
    • Sean Hogan
      Sean Hogan on 07 Nov 14
       
      So in the slower transport of RABV without the endosome the interaction between the negative phosphoprotein P and dynein must be sufficient for transport down the microtubules. 
  • slgoogin8981 on 03 Nov 14
     
    Friday 11-7-14, paper
apopp10

Rabies Virus Hijacks and Accelerates the p75NTR Retrograde Axonal Transport Machinery - 2 views

www.ncbi.nlm.nih.gov/...PMC4148448

shared by apopp10 on 07 Nov 14 - No Cached
  • the RABV phosphoprotein P directly interacts with a dynein light chain [11], [12], suggesting a mechanism whereby this interaction is key to RABV's retrograde trafficking. However, studies on the retrograde transport of RABV enveloped virions [14] and infection of the CNS from the periphery with dynein light chain binding defective virus mutants [13] already showed that such an interaction is not essential for retrograde axonal transport of the virus
    • jpolanco10
      jpolanco10 on 07 Nov 14
       
      It says that this mechanism is key, yet the mutations with the defect show this is not essential. Is something else that is facilitating the trafficking with the phosphoprotein P?
  • In order to illustrate the differences leading to faster transport of RABV compared to NGF, we proceeded to inquire whether internalization of these ligands occurs over similar time frames. To this end, we performed a series of live imaging experiments using TIRF microscopy, and tracked fluorescent RABV or NGF particles at the axonal growth cone. Distinct features of the TIRF evanescent wave allow us to limit our view to the basal surface, an ideal set up for viewing internalization processes occurring at axon tips.
    • apopp10
      apopp10 on 07 Nov 14
       
      Why is the basal surface ideal for viewing internalization processes? It also seems that the RABV is faster by just a few seconds according to figure 3. What implications does this have for the virus
Casey Finnerty

Are all virus particles infectious? - 0 views

www.virology.ws/...all-virus-particles-infectious

shared by Casey Finnerty on 06 Nov 14 - No Cached
  • A high particle-to-pfu ratio is sometimes caused by the presence of noninfectious particles with genomes that harbor lethal mutations or that have been damaged during growth or purification. Another explanation is that although all viruses in a preparation are in fact capable of initiating infection, not all of them succeed because of the complexity of the infectious cycle. Failure at any one step in the cycle prevents completion. A high particle-to-pfu ratio does not indicate that most particles are defective, but that they failed to complete the infection.
Casey Finnerty

'Binding, bending and bonding': polypurine tract-primed initiation of plus-strand DNA s... - 0 views

www.sciencedirect.com/...S1357272504000949

HIV

shared by Casey Finnerty on 06 Nov 14 - No Cached
  • Casey Finnerty on 06 Nov 14
     
    This review describes nicely HIV replication and the role of the PPTs.
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