Skip to main content

Home/ WSU Virology/ Group items tagged transmission

Rss Feed Group items tagged

Sarah Muncy

ScienceDirect.com - Vaccine - Intranasal and intramuscular immunization with Baculoviru... - 0 views

  • An anti-malarial transmission-blocking vaccine (TBV) that prevents fertilization and/or ookinete/oocyst development within the mosquito is an attractive strategy to limit the transmission of malaria
  • The present study used this system to generate a Plasmodium vivax transmission-blocking immunogen (AcNPV-Dual-Pvs25).
  • Plasmodium vivax
  • ...10 more annotations...
  • A variety of expression vectors (e.g., Escherichia coli, Pichia pastoris and DNA) have been used to express Pvs25 protein which has been administered alone or in combination with adjuvants
  • To date these studies suggest that the recombinant protein currently requires both not only linear, but conformation dependent epitopes, and a strong adjuvant to induce transmission-blocking antibodies.
  • Intranasal and intramuscular immunization with Baculovirus Dual Expression System-based Pvs25 vaccine substantially blocks Plasmodium vivax transmission
  • Recently, we have developed a new vaccine vector system based on the baculovirus Autographa californica nucleopolyhedrosis virus (AcNPV) termed the “Baculovirus Dual Expression System”, which drives expression of vaccine candidate antigens by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammalian-derived CMV promoters. It has been shown that AcNPV, an enveloped double-stranded DNA virus that naturally infects insects, possesses strong adjuvant properties that can activate dendritic cell-mediated innate immunity
  • Mucosal vaccines have several attractive features compared with parenteral vaccines (e.g., safety, cost-effectiveness and ease of administration), but studies on their use have been limited almost exclusively to protection against mucosally transmitted pathogens. We provide evidence that i.n. immunization is a feasible alternative for preventing malaria, which is transmitted through non-mucosal routes
  • These results are consistent with our previous work showing that intranasal immunization with the baculovirus-based vaccine induced strong systemic humoral immune responses with high titres of antigen-specific antibodies and conferred complete protection against malaria blood-stage challenge
  • which can induce immunological memory against heterologous antigens in a rodent model; however, it is precluded from clinical use due to its enterotoxicity and potential hazardous effects on olfactory nerves [22]. In contrast, a baculovirus-based delivery system may offer an attractive immunization method, as AcNPV exhibits low cytotoxicity and is incapable of replication in mammalian cells
  • The data described here adds to previously presented data showing the significant potential of the baculovirus dual expression system against the blood stages of the parasite
  • but also demonstrates clearly its ability to induce antibodies against the ookinete surface protein Pvs25, and to elicit a transmission-blocking immune response against the P. vivax isolates from endemic areas, and a transgenic rodent malaria parasite model in preliminary studies.
  • One was SMFA on peripheral blood from P. vivax infected patients.
  •  
    Reference paper #2. Gave me information on malaria and baculoviruses.
laceemarie

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

  • 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
       
      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
       
      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
       
      Why is this an important site for variation?
    • laceemarie
       
      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)
  •  
    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

    • Sarah Muncy
       
      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.
  •  
    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

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission ... - 5 views

  •  
    This paper by the Kawaoka group is the first report of an H5N1 virus that is transmissible by aerosol between mammals.
Casey Finnerty

Coevolution of hosts and parasites. [Parasitology. 1982] - PubMed - NCBI - 0 views

  •  
    This paper is a seminal publication in our understanding of host-parasite coevolution. The authors suggest that virulence will be maintained if necessary for parasite transmission.
Casey Finnerty

For Young Scientists, A Wild Ride - 0 views

  •  
    This article discusses the drama behind the scenes of the debate over publication of the H5N1 transmissibility studies and the effect it had on young scientists carrying out the work.
Casey Finnerty

What We're Afraid to Say About Ebola - NYTimes.com - 9 views

  • The first possibility is that the Ebola virus spreads from West Africa to megacities in other regions of the developing world.
  • The second possibility is one that virologists are loath to discuss openly but are definitely considering in private: that an Ebola virus could mutate to become transmissible through the air.
  • The current Ebola virus’s hyper-evolution is unprecedented; there has been more human-to-human transmission in the past four months than most likely occurred in the last 500 to 1,000 years. Each new infection represents trillions of throws of the genetic dice.
  • ...1 more annotation...
  • In 2012, a team of Canadian researchers proved that Ebola Zaire, the same virus that is causing the West Africa outbreak, could be transmitted by the respiratory route from pigs to monkeys, both of whose lungs are very similar to those of humans.
Casey Finnerty

VIRULENCE NOT ONLY COSTS BUT ALSO BENEFITS THE TRANSMISSION OF A FUNGAL VIRUS - Bryner ... - 0 views

  •  
    This paper provides experimental support for the ideas of Anderson and May on host-parasite coevolution.
Matthew Marshall

Dengue: a continuing global threat : Article : Nature Reviews Microbiology - 0 views

  •  
    Follow up research subsequent to viewing Dr. Eva Harris's Lecture, Dengue Fever: Breaking Epidemic Cycles. Research focused on mechanisms behind severe dengue forms DHF and DSS. Figure 1 in paper is from this article.
Sean Hogan

PLOS Pathogens: Different Modes of Retrovirus Restriction by Human APOBEC3A and APOBEC3... - 22 views

  • One such family of restriction factors is the apolipoprotein B editing complex 3 (A3) cellular cytidine deaminases (CDA). While A3 genes are found in all mammals, their number differs from species to species. For example, humans have 7 A3 genes (A3A to A3H) while mice have only one gene. All proteins in this family contain at least one CDA domain that deaminates carbon 4 of cytidine in single-stranded DNA, resulting in a uracil that causes G to A transitions in the opposing strand [3].
    • alexridesducati
       
      Can these genes be exploited for antiviral therapy and if so, can it be done without harm to the host due to mutations?
  • viral cDNA accumulation
  • Packaging of A3G into virions is counteracted by HIV Vif (viral infectivity factor) protein. In virus-producer cells, Vif binds to A3G as well other A3 family members, and recruits cellular E3 ubiquitin ligase complexes, leading to ubiquitination and subsequent proteasomal degradation, thereby preventing packaging of A3G into budding virions [12]–[14]. Lentiviral Vif proteins show strong species-specificity. For example, HIV-1 Vif counteracts human A3G but only certain simian A3G homologues [15], [16]; it also does not interact with mouse A3 [17].
  • ...12 more annotations...
  • Other members of the A3 family are believed to affect other exogenous viruses as well as endogenous retrovirus/retroelement movement within the genome. In particular, human A3A is a potent inhibitor of IAP and MusD and other retrotransposons such as LINE-1 and this inhibition is CDA-independent, at least in cultured cells [18]–[20]. A3A also inhibits adeno-associated virus replication, a nuclear-replicating parvovirus, via CDA-independent means [20]. In monocytes, A3A restricts HIV-1 infection and the decrease in A3A levels that occurs during monocyte-to-macrophage development is concomitant with increased susceptibility to HIV-1 infection [21]. A3A is not packaged into HIV virions and is thought to restrict infection by targeting incoming virus [22]–[24]. In contrast, A3A is packaged in human T-lymphotropic virus type-I virions and restricts infection, at least in transfected cells [25]. A3A preferentially deaminates cytidines that are in a TC motif [26].
  • Different A3 family members block infection by diverse retroviruses from different species, including HIV-2 [27], porcine endogenous retrovirus [28], [29], xenotropic, Friend (F-MLV) and Moloney murine leukemia virus (M-MLV) [30]–[32] and mouse mammary tumor virus (MMTV) [33]. Additionally, A3 proteins may restrict other virus families, including parvoviruses [20], [34], hepatitis B virus [35]–[37], papillomaviruses [38] and herpes simplex virus I [39]. Thus, it has been suggested that A3 proteins exist, at least in part, to prevent zoonotic transmission of viruses [40].
  • Here, we show that transgenic mice expressing the human A3A or A3G proteins restrict murine retrovirus infection in vivo in disparate ways. A3G was packaged into virions in vivo, leading to the deamination of both MLV and MMTV viral genomes. In contrast, A3A was not packaged, and appeared to restrict infection in a largely CDA-independent manner. Finally, we show that Vif/A3G interactions can be studied in this in vivo model, thus providing a potentially useful system for the analysis of small molecule inhibitors of A3 proteins and Vif.
  • To determine the level of transgene expression, we first isolated RNA from different tissues, including peripheral blood mononuclear cells (PBMCs), and performed reverse-transcribed real-time quantitative PCR (RT-qPCR). RNA from human H9 cultured cells and human and C57BL/6 mouse PBMCs served as controls. For each transgene, there was one high- (A3Ghigh, A3Ahigh) and one low- (A3Glow, A3Alow) expressing strain, defined by their relative expression in lymphoid tissues. The A3Ghigh strain expressed higher levels of the transgene than the endogenous mouse gene in spleen and thymus, but similar A3G levels in mouse and human PBMCs, while the A3Glow strain expressed approximately 10-fold lower levels in these tissues (Figure 1A). In contrast, the A3Ahigh strain expressed similar or lower levels than mouse A3; there was also about 2-fold lower expression of A3A in mouse PBMCs than in human PBMCs (Figure 1B). The A3Alow strain had very low but detectable levels of expression in several tissues. Since the β-actin regulatory region was used, transgene expression was seen in many tissues and in several at levels higher than endogenous mouse A3 (e.g. heart, brain and liver) (Figure 1A and 1B). We also performed western blots on different tissues from the 4 different mouse strains, using antiserum that detects both A3A and A3G. The relative protein expression levels were similar to that seen at the RNA level (Figure S1A and S1B).
  • We next determined if the in vivo-produced A3A and A3G proteins were functionally active. Extracts were prepared from primary splenocyte cultures and equal amounts (total protein concentration/volume) were incubated with FAM-labeled substrates containing the A3A- or A3G-preferred target sequence (S50-TTC and S50-CCC, respectively). As controls, we also performed these assays with extracts prepared from 293T cell lines transfected with A3A or A3G. Activity could be readily detected in transgenic mice expressing high levels of A3A or A3G. Further, in accord with the known specificity of the cytidine deaminases, extracts from the A3Ahigh mice deaminated the TTC- more efficiently than CCC-containing substrates, while those from A3Ghigh mice more efficiently deaminated the CCC substrate (Figure 2). For both A3Alow and A3G low, trace amounts of activity were detectable with the preferred substrates, while no activity was detectable with either endogenous mA3 or from mA3 knockout splenocytes. No deaminase activity was detected with WT mouse extracts, perhaps because the mouse protein has lower overall activity or expression. These data show that the transgenic mice expressed catalytically active human deaminases in these heterologous cells.
  • Humans have 7 APOBEC3 genes and determining how each specifically functions to inhibit retroviruses like HIV is complicated, because all 7 can be produced in a given cell type or tissue.
    • laceemarie
       
      What cell/tissue type(s) are these APOBEC3 genes naturally turned on in? 
  • To overcome this limitation, we made transgenic mice that express two of the human proteins, APOBEC3A and APOBEC3G in mice that do not express their own APOBEC3. These mice were able to effectively block infection by several mouse retroviruses
    • laceemarie
       
      What cell type(s) did they use? Does it matter which?
  • We were unable to perform similar assays with in vivo produced MMTV, because the only cell-free virus in mice is found in milk and mammary tumors and we have not yet established breeding colonies of virus-infected human A3 transgenic mice.
    • laceemarie
       
      Was this a screw up, or is it not that important to look at assays with in vivo produced MMTV. And by "not yet," does that mean they are going to? I feel like if your going to use this virus in your experimental studies, you should figure out ways to perform the assays, regardless of how you get the virus. It would appear that they knew this information before hand, so maybe an assay on MMTV is less relevant. 
    • laceemarie
       
      *you're
  • A3G and A3A inhibit retrovirus infection by different means.
    • becky214
       
      Since they use different means of inhibition, do they work together to prevent infection? Or is an and either/or type scenario?
  • Two A3A and A3G mouse strains each were generated, expressing levels of these proteins within the range or at levels lower than that seen in human cells. This likely has relevance to what occurs in individual humans, where non-coding region polymorphisms in A3 genes alter expression levels and may influence progression to HIV-induced disease
    • laceemarie
       
      Could this have something to do with how HIV works in the HIV controllers? Where they still exhibit virus particles, but at a lower amount, don't necessarily spread the virus as much, and don't exhibit as intense of HIV symptoms?
    • ameliaobert
       
      If A3A is less clear, but does not get packaged, where must the A3A involvement with the incoming virus be located (for myeloid cells)? As well as if it is known to use retroelement retotransposition and replication inhibiton in paraoviruses by nh2 to oh independent means, how does the A3A know to be signlle to change the structure of cystine?
  • An additional limitation of previous studies done on human A3 proteins is the reliance on transfecting constructs expressing A3 proteins, which may not reflect the endogenous levels of a protein expression found in vivo
    • Sean Hogan
       
      Couldn't they mimic the in vivo environment by overexpressing necessary proteins in the host?
  •  
    Focus paper for retrovirus presentation.
  •  
    This will be the focus paper for 11/14.
Casey Finnerty

Mapping the zoonotic niche of Ebola virus disease in Africa | eLife - 0 views

  • Increasing population sizes and international connectivity by air since the first detection of EVD in 1976 suggest that the dynamics of human-to-human secondary transmission in contemporary outbreaks will be very different to those of the past.
1 - 20 of 23 Next ›
Showing 20 items per page