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Casey Finnerty

Recovery of genetically defined murine norovirus in tissue culture by using a fowlpox v... - 1 views

vir.sgmjournals.org/...2091.full

norovirus

shared by Casey Finnerty on 22 Sep 14 - No Cached
  • Previous calicivirus reverse-genetics systems have relied on the transfection of either in vitro-transcribed, 5′-capped calicivirus genomic RNA (Chang et al., 2005; Sosnovtsev & Green, 1995) or cDNA constructs, followed by delivery of T7 RNA polymerase using a VACV recombinant (Sosnovtsev et al., 2002; Thumfart & Meyers, 2002). A recent report on rabbit hemorrhagic disease virus (RHDV) has also demonstrated that in vitro-transcribed, uncapped RNA is infectious when transfected into cells or delivered directly to the liver in vivo (Liu et al., 2006). Attempts to recover MNV by using any of these established approaches failed to produce infectious virus (data not shown).
  • Casey Finnerty on 22 Sep 14
     
    This paper contains very good background on the development of the MNV reverse genetics system. The norovirus genome is uncappped, but transfection with uncapped mRNAs does NOT produce many progeny virions.
apopp10

The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation - 11 views

www.ncbi.nlm.nih.gov/...PMC3235490

shared by apopp10 on 14 Nov 14 - No Cached
  • Yet a small number of people demonstrate sustained ability to control HIV replication without therapy. Such individuals, referred to as HIV controllers, typically maintain stable CD4+ cell counts, do not develop clinical disease, and are less likely to transmit HIV to others (2).
    • laceemarie
      laceemarie on 14 Nov 14
       
      This is really cool! I have not heard of this until now. Have these people been studied to find out why this occurs? Is it because of the genetics of the person or a certain mutation in the virus? And the key words here are "less likely." That's a pretty broad statement - "less likely" meaning how likely?
    • slgoogin8981
      slgoogin8981 on 24 Nov 14
       
      It is interesting to see that there are 3 allelic variants that correlate with disease prognosis, but how does this information benefit society? We can't change peoples genetic so to alter their prognosis. Is this just a benefit to know what medications would be most beneficial with the least amount of side effects?
  • Abstract
    • Sean Hogan
      Sean Hogan on 02 Dec 14
       
      Presentation Paper 11/14
  • ...2 more annotations...
  • Although variation in the entire HLA protein is involved in the differential response to HIV across HLA allotypes, the major genetic effects are condensed to the positions highlighted in this study, indicating a structural basis for the HLA association with disease progression that is probably mediated by the conformation of the peptide within the class I binding groove.
    • becky214
      becky214 on 06 Dec 14
       
      If variation in the HLA protein results in different responses to HIV, does it also cause different responses to antiviral HIV drugs?
    • apopp10
      apopp10 on 08 Dec 14
       
      So it's only the amino acid position that accounts for the SNP and HLA association signals? It does not matter what amino acid you place there? Individual amino acid chemistry will have no affect on it?
kwedul

A Multicomponent Animal Virus Isolated from Mosquitoes: Cell Host & Microbe - 68 views

www.cell.com/...S1931-3128(16)30310-9

shared by kwedul on 02 Sep 16 - Cached
  • reverse genetics system
    • Casey Finnerty
      Casey Finnerty on 02 Sep 16
       
      Please be ready to explain why reverse genetics was a necessary approach for studying this virus.
  • GCXV
    • Casey Finnerty
      Casey Finnerty on 14 Sep 16
       
      Here is an example of a stickie note.
  • Viral replication was detected in three mosquito cell lines and in intrathoracically inoculated adult female mosquitoes
  • ...14 more annotations...
  • Selective degradation with RNase I demonstrates that GCXV has a single-stranded RNA genome.
    • Casey Finnerty
      Casey Finnerty on 19 Sep 16
       
      RNaseI is specific for ssRNA.
  • reverse genetics system
  • Multicomponent plant viruses were recognized on the basis of deviations from the expected relationship between infectious dose and the number of lesions on infected leaves (i.e., exhibiting multi-hit rather than single-hit kinetics; Flint et al., 2009xPrinciples of Virology Volume I: Molecular Biology. Flint, S.J., Enquist, L.W., Racaniello, V.R., Skalka, A.M., Barnum, D.R., and de Evaluación, E. See all References, Sánchez-Navarro et al., 2013xEffects of the number of genome segments on primary and systemic infections with a multipartite plant RNA virus. Sánchez-Navarro, J.A., Zwart, M.P., and Elena, S.F. J. Virol. 2013; 87: 10805–10815Crossref | PubMedSee all References).
    • jsackett13
      jsackett13 on 19 Sep 16
       
      This was explained in the blog article.
  • of any other group of organisms (
    • aceastep
      aceastep on 19 Sep 16
       
      wow
  • no Illumina reads aligned to the segment 5 sequences from the other isolates, and no contigs from ACH27 exhibited significant similarity to the segment 5 sequences from the other isolates. Therefore, segment 5 appears to be absent from ACH27 and TR7094.
  • However, only four segments were assembled for ACH27 and TR7094 (genome size ∼10.6 kb). For these two isolates, the four assembled segments corresponded to the four largest segments assembled in the other isolates (Figure 1Figure 1, segments 1–4).
  • The phylogeny inferred from segment 5 is also inconsistent with those of the other segments. In addition to the absence of this segment in TR7094 and ACH27, this segment exhibited very low levels of nt divergence (0.4%–2.3%), with most sequence variations only present in a single isolate.
  • with each genome segment separately packaged into virions. Although multicomponent genomes are relatively common among RNA viruses that infect plants and fungi, this method of genome organization has not previously been seen in animal viruses (
    • kwedul
      kwedul on 21 Sep 16
       
      Is this the only thing required for a genome to be considered multicomponent?
  • RNA extracted from purified GCXV particles confirmed the presence of a segmented genome (
    • kwedul
      kwedul on 21 Sep 16
       
      So what exactly is it about this purified GCXV that shows it is segmented?
  • The mosquito pools for both ACH27 and TR7094 contained multiple viruses capable of replicating in mosquito cells, so we were unable to obtain pure cultures for these isolates (
    • kwedul
      kwedul on 21 Sep 16
       
      What is it about there being multiple viruses capable of replicating that made them unable to obtain pure cultures for the isolates?
  • Nuclease digestion assays (Figure 1Figure 1B), along with 5′ and 3′ rapid amplification of cDNA ends (RACE), confirmed that all five genome segments were single-stranded, positive-sense RNA (ssRNA+).
    • kwedul
      kwedul on 21 Sep 16
       
      What about these tests confirms all five genome segments were single-stranded positive-sense RNA?
  • all five segments, (2) segments 1–4, and (3) segments 2–5
    • kwedul
      kwedul on 21 Sep 16
       
      Why did they use these three combinations?
  • the number of plaques decreased more quickly than expected with dilution of the inoculant) (
    • kwedul
      kwedul on 21 Sep 16
       
      Why? What is the significance of this?
  • segments 1–5 (passage 1) and segments 1–4 (passage 2)
    • kwedul
      kwedul on 21 Sep 16
       
      What about a second passage, including 1-4, makes it brighter?
Casey Finnerty

We Now Have the Cure for Hepatitis C, but Can We Afford It? - Scientific American - 13 views

www.scientificamerican.com/...patitis-c-but-can-we-afford-it

hepatitis medicine antiviral HCV

shared by Casey Finnerty on 09 Dec 14 - No Cached
  • Later this year the U.S. Food and Drug Administration is expected to approve a new pill that can cure hepatitis C
  • It will contain two drugs, one of which is already available at $1,000 per dose, or $84,000 for a complete 12-week course. The dual-drug combination will likely cost even more
  • They also determined that the virus's genes mutate very fast—a process that has generated several equally successful varieties, called genotypes, and rendered an effective vaccine impossible to create so far.
  • ...7 more annotations...
  • its genetic material, which is made up of RNA
  • After several false starts, researchers at Vertex Pharmaceuticals, in collaboration with others, developed a protease inhibitor known as telaprevir, while scientists at Schering-Plough (which merged with Merck in 2009), created one called boceprevir.
  • The medications had harsh side effects and worked only for those patients with a particular genetic variant of the virus known as genotype 1
  • What scientists had learned from their earlier research, however, was that inactivating an enzyme or protein was not enough. To stop hepatitis C, any effective drug also had to incorporate itself into the virus's genetic code, where it would need to halt the virus's ability to make new copies of its genes and thus to make new virus.
  • Michael Sofia, then at Pharmasset, solved the problems by adding two compounds known as esters to the analogue.
  • During sofosbuvir's development, they had studied other drugs that inhibited different viral proteins and that might eliminate the need for continued use of interferon and ribavirin.
  • It is this combination, mixed in a single daily pill, that industry watchers expect the FDA to approve by October 2014. It heralds a new era of curative treatment for patients with hepatitis C. Similar drugs that work equally well for all genotypes are now in the final stages of clinical development.
Sarah Muncy

High levels of genetic variation within Helicover... [Arch Virol. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...22878553

shared by Sarah Muncy on 17 Sep 12 - No Cached
  • Sarah Muncy on 17 Sep 12
     
    Is it that the virus itself has a great deal of genetic diverisity, or is it somehow an emergent property with it and the host organism? Insects are arguably the most diverse organisms on earth, doesn't it seem reasonable to expect baculoviruses to be equally diverse? Even if they're simply diverse because they've evolved (or whatever terms apply to these abiotic "Creatures") together, each one-upping each other as natural selection has operated- it's pretty cool.
Casey Finnerty

Cooperative interactions in the West Nile virus mutant swarm - 0 views

www.ncbi.nlm.nih.gov/...PMC3358237

virology population biology genomics genetics

shared by Casey Finnerty on 25 Sep 12 - No Cached
  • In addition, our data demonstrate that increasing levels of co-infection can lead to widespread strain complementation, which acts to maintain high levels of phenotypic and genetic diversity and potentially slow selection for individual variants. Lastly, we show that cooperative interactions may lead to swarm fitness levels which exceed the relative fitness levels of any individual genotype.
Sarah Muncy

The HIV Virus: A Possible Cure for Leukemia? | Yahoo! Health - 0 views

health.yahoo.net/...v-virus-possible-cure-leukemia

shared by Sarah Muncy on 12 Dec 12 - No Cached
  • It's important to note that the T-cells are removed from the patient before being bioengineered with the HIV virus
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Why is it important to note that the disabled virus isn't injected into the patient? It's function isn't like chemotherapy at all- why even make the comparison?
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Is there some reason they use T cells only? Are they trying to target T cells, but not dendritic cells or macrophages?
  • therapies that involve the reprogramming of a patient’s immune system, may also eventually be used to fight cancerous breast and prostate tumors.
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      What about lupus, or even allergies for that matter?
  • ...1 more annotation...
  • Within hours
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Within hours?!
  • Sarah Muncy on 12 Dec 12
     
    Whoa. If someone is doing HIV- this may be helpful. The virus is being used as a delivery device for genetics to reprogram lymphocytes. They're like biological nanorobots.
laceemarie

Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets - 12 views

www.sciencemag.org/...1534.full

shared by laceemarie on 04 Dec 12 - No Cached
  • The MBCS in HA can be cleaved by ubiquitously expressed host proteases; this cleavage facilitates systemic virus replication and results in mortality of up to 100% in poultry (9, 10).
  • Although limited A/H5N1 virus transmission between persons in close contact has been reported, sustained human-to-human transmission of HPAI A/H5N1 virus has not been detected (13–15).
    • Casey Finnerty
      Casey Finnerty on 05 Sep 14
       
      Could this not be happening?
  • The viruses that caused the major pandemics of the past century emerged upon reassortment (that is, genetic mixing) of animal and human influenza viruses (22).
    • Casey Finnerty
      Casey Finnerty on 05 Sep 14
       
      How many pandemics are they talking about? Put another way, for how many pandemics in human history, do we have the virus on hand to analyze?
  • ...2 more annotations...
  • Influenza A viruses show pronounced genetic variation of the surface glycoproteins HA and NA
    • slgoogin8981
      slgoogin8981 on 05 Sep 14
       
      Why is this an important site for variation?
    • laceemarie
      laceemarie on 08 Sep 14
       
      To be able to bind to a variety of different cells?
  • the factors that determine airborne transmission of influenza viruses among mammals, a trait necessary for a virus to become pandemic, have remained largely unknown (18–21)
  • Casey Finnerty on 04 Sep 14
     
    This is the H5N1 mammal transmissibility paper from the Fouchier group.
jiyoung yoon

Association of HIV Diversity and Survival in HIV-Infected Ugandan Infants - 10 views

www.plosone.org/...10.1371%2Fjournal.pone.0018642

hiv genetic disease virology

shared by jiyoung yoon on 09 Sep 12 - No Cached
    • Sarah Muncy
      Sarah Muncy on 10 Sep 12
       
      Ha, so again, like an organism. Where a population has a great deal of genetic diversity, there are more traits onto which natural selection can act. The more diverse the HIV is at this given stage means a failure in this case though, as the host dies and cannot transmit the disease. Strange.
  • Casey Finnerty on 10 Sep 12
     
    That's a really cool observation, Sarah! It's really all about transmission. Since HIV is (primarily) sexually transmitted, infection in infants (via transovarial transmission) may be considered a dead end for the virus. Perhaps vertical transmission is an aberrance. If HIV would evolve into a less virulent form, perhaps vertical transmission would become more important. Just sayin'...
Casey Finnerty

Quasispecies diversity determines pathogenesis throug... [Nature. 2006] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...16327776

virology genomics population biology genetics

shared by Casey Finnerty on 25 Sep 12 - No Cached
  • Analysis of viruses isolated from brain provides direct evidence for complementation between members in the quasispecies, indicating that selection indeed occurs at the population level rather than on individual variants.
Casey Finnerty

Functional importance of deletion mut... [Appl Environ Microbiol. 2005] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...16085811

virology baculoviruses genomics population biology genetics

shared by Casey Finnerty on 25 Sep 12 - No Cached
  • Casey Finnerty on 25 Sep 12
     
    This paper shows the importance of genotypic diversity for baculovirus populations, particularly in terms of pathogenicity.
Sarah Muncy

Koala pandemic genetics: Viruses have inserted themselves into the human genome 31 time... - 1 views

www.slate.com/...themselves_into_the_human.html

shared by Sarah Muncy on 07 Dec 12 - No Cached
  • And in future generations, those genes will gradually mutate and lose their ability to make new viruses. Eventually, the koala retrovirus will become extinct. All that will remain will be its imprisoned DNA.
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Wow- they seem pretty confident in what will happen, what mutations will take place and what their effects will be. Hmm.
  • In many koalas, the virus’ genes aren’t present just in the immune cells. The koalas carry the virus genes in every cell of their bodies, from their vestigial tails to their snub noses and in every organ in between
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Wait, so if the virus can infect EVERY kind of cell, it must either have lots of receptors or a wide range of receptor specificity, right? If it's THAT much of a generalist, then surely it must be infectious to other organisms- or at least capable of entry. Does that mean it's at risk for spread in other mammals?
  • Koalas had long been known to have terrible health
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      I've never heard of a wild animal population having "terrible health." That's something you hear about in pure-bred populations, such as with pure bred dogs. If they have notoriously poor health, why do they exist?
Sarah Muncy

A Breakthrough Against Leukemia Using Altered T-Cells - NYTimes.com - 1 views

www.nytimes.com/...mia-using-altered-t-cells.html

virology cancer immunology microbiology

shared by Sarah Muncy on 10 Dec 12 - No Cached
  • To perform the treatment, doctors remove millions of the patient’s T-cells — a type of white blood cell — and insert new genes that enable the T-cells to kill cancer cells. The technique employs a disabled form of H.I.V. because it is very good at carrying genetic material into T-cells. The new genes program the T-cells to attack B-cells, a normal part of the immune system that turn malignant in leukemia.
  • The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells
  • cytokine-release syndrome, or cytokine storm
  • ...5 more annotations...
  • Dr. June knew that a drug could lower IL-6
  • tocilizumab
  • the altered T-cells persist in the bloodstream
  • The researchers are not entirely sure why the treatment works, or why it sometimes fails.
  • It is not clear whether a patient’s body needs the altered T-cells forever. The cells do have a drawback: they destroy healthy B-cells as well as cancerous ones, leaving patients vulnerable to certain types of infections, so Emma and the other patients need regular treatments with immune globulins to prevent illness.
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      I was wondering when they'd get to the consequences of killing off the B cells- that's huge.
  • Sarah Muncy on 12 Dec 12
     
    That's so funny- I just saw the update email and Dr. Finnerty also saw this topic (a different article) and posted it, too!)
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