Virology News
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Topical news snippets about viruses that affect people. And other things.
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PLoS Pathogens: Mutation and Selection of Prions

PLoS Pathogens: Mutation and Selection of Prions | Virology News | Scoop.it

Prion diseases, or transmissible spongiform encephalopathies (TSEs), occur naturally in several species, including humans, cattle, sheep, and deer, and can be transmitted experimentally to many others. Typically, incubation times are relatively long, extending to 40 years or more in humans; however, after appearance of clinical symptoms, death mostly ensues within less than a year, as a consequence of neurodegeneration accompanied by accumulation of abnormal conformers of the host protein PrP. Natural transmission usually occurs perorally, as exemplified by the kuru epidemic among the Fore people of Papua New Guinea, attributed to cannibalistic practices; the bovine spongiform encephalopathy (BSE) epizootic in the United Kingdom at the end of last century, caused by feeding of contaminated meat-and-bone meal to cattle; or the current epizootic of chronic wasting disease afflicting cervids in 19 states of the United States. Transmission of BSE prions to young humans gave rise to a limited outbreak of a novel illness, variant Creutzfeldt-Jakob disease (vCJD), almost exclusively in the UK. Sporadic cases of prion disease occur at very low frequency in human populations (sCJD) and in cattle herds (atypical BSE), and are attributed to spontaneous generation of prions in the affected individuals. Finally, familial forms of human prion disease are linked to a variety of different, dominant mutations in the PRNP gene, and while afflicted families are rare, penetrance is very high.

 

Very nice review from an authority in the field.

Prion image courtesy of Russell Kightley Media

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The Secret Life of Viral Entry Glycoproteins

The Secret Life of Viral Entry Glycoproteins | Virology News | Scoop.it

Survival of infection with Ebola virus (EBOV) depends on the ability of the host to mount early and strong immune responses [1], [2]. However, given that EBOV cases are associated with 40%–90% human mortality, EBOV has developed intricate solutions to human immunological defenses. Enveloped viruses, like EBOV, must deposit their genetic material within a cell to ensure their propagation. The roles of viral envelope glycoproteins in mediating virus attachment to host cells and catalyzing the subsequent fusion of the viral and host plasma membranes have been well described (reviewed in [3]). Given the limited number of genes in EBOV and other viruses, it stands to reason that these conformationally labile glycoproteins are also involved in more than just the initial steps of a productive infection. There is strong evidence that viral entry glycoproteins (GP) are modulators of host antiviral defenses (Table 1). In this article, we discuss our current structural understanding of the functions of envelope entry glycoproteins in immune evasion using EBOV as our example.

 
Ed Rybicki's insight:

Nice review on a very interesting and important topic - and highlights how viral entry proteins double as immune evasion agents.

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China H7N9 Joint Mission Report 2013 (WHO)

Ed Rybicki's insight:

An important document - because it lays out in detail just what a high-level team that went to China found during their travels.  And it is disturbing: the virus has 6 internal genes of H9N2, with the H7 HA and N9 NA - the first time the latter has been seen in humans.  I note that H9N2 keeps popping up in humans, but is not so nasty: the H7N9, however, is a low pathogenicity virus in chickens, but severe in humans.

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India announces development of $1 rotavirus vaccine

India announces development of $1 rotavirus vaccine | Virology News | Scoop.it

The Government of India’s Department of Biotechnology (DBT) and Bharat Biotech have announced the development of a rotavirus vaccine that will be sold at $1 per dose, once approved. Results from a Phase III clinical trial showed that the ROTAVAC® vaccine decreased the incidence of severe rotavirus diarrhoea by 56% during the first year of life, and the protection conferred by the vaccine also continued into the second year of life. The clinical trial enrolled 6,799 infants across three sites in India.


The vaccine’s development resulted from a unique partnership between Indian and international researchers, with partners including DBT, Bharat Biotech, the US National Institutes of Health (NIH), the US Centers for Disease Control and Prevention (CDC), Stanford University School of Medicine, and PATH.


Rotavirus graphic courtesy of Russell Kightley Media

Ed Rybicki's insight:

We need to do this here...!

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Potential for H3N2 influenza pandemic

Potential for H3N2 influenza pandemic | Virology News | Scoop.it

The 2009 swine-origin H1N1 influenza, though antigenically novel to the population at the time, was antigenically similar to the 1918 H1N1 pandemic influenza, and consequently was considered to be [ldquo]archived[rdquo] in the swine species before reemerging in humans. Given that the H3N2 is another subtype that currently circulates in the human population and is high on WHO pandemic preparedness list, we assessed the likelihood of reemergence of H3N2 from a non-human host. Using HA sequence features relevant to immune recognition, receptor binding and transmission we have identified several recent H3 strains in avian and swine that present hallmarks of a reemerging virus. IgG polyclonal raised in rabbit with recent seasonal vaccine H3 fail to recognize these swine H3 strains suggesting that existing vaccines may not be effective in protecting against these strains.


Vaccine strategies can mitigate risks associated with a potential H3N2 pandemic in humans.

Ed Rybicki's insight:

No-one think of H3N2...except, as it happens, these folk - who have shown quite convincingly that circulating strains of H3N2 in birds and pigs would be quite capable of avoiding vaccine-conferred immunity, and potentially of causing a pandemic, if they reassorted with human-infecting viruses.  

 

I can't help but feel that there are several ticking influenza pandemic time bombs out there...H5N1, H7N9, and now H3N2.

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The Lurker: How A Virus Hid In Our Genome For Six Million Years

The Lurker: How A Virus Hid In Our Genome For Six Million Years | Virology News | Scoop.it
In the mid-2000s, David Markovitz, a scientist at the University of Michigan, and his colleagues took a look at the blood of people infected with HIV. Human immunodeficiency viruses kill their host...
Ed Rybicki's insight:

Thanks to @AJCann for pointing this out.

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Development of human papillomavirus chimaeric L1/L2 candidate vaccines

Development of human papillomavirus chimaeric L1/L2 candidate vaccines | Virology News | Scoop.it

Recombinant human papillomavirus (HPV) virus-like particle (VLP) vaccines based on the L1 capsid protein have been shown to be efficient prophylactic vaccines, albeit type-specific. As a first step to investigate the feasibility of extending protection against non-vaccine types, HPV-16 L1 chimaeras were generated. The region downstream of L1 amino acid (aa) 413 was replaced with selected cross-neutralising epitopes (aa 108-120; 56-81 and 17-36) derived from the HPV-16 L2 protein, generating proteins designated SAF, L2.56 and L2.17, respectively. The chimaera L1BPV containing BPV-1 L2 peptide aa 1-88 was similarly constructed. The chimaeras were evaluated for expression in insect cells; their ability to form particles was studied by electron microscopy, and their immunogenicity was evaluated in mice. SAF, L2.56 and L2.17 proteins were expressed to high concentrations in insect cells and elicited HPV-16 pseudovirus-neutralising anti-L1 antibodies. L2.56 and L2.17 also elicited anti-L2 antibodies. L1BPV was a poor vaccine candidate due to low levels of expression with concomitant lack of immunogenicity. All chimaeras assembled into tertiary structures. The results indicate that chimaeric L1 vaccines incorporating cross-neutralising L2 peptides could be promising second-generation prophylactic HPV vaccine candidates.

 Cervical cancer graphic courtesy Russell Kightley Media
Ed Rybicki's insight:

We keep grinding on...someday, someone will be interested!

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Medicago successfully produces VLP vaccine candidate for H7N9 virus

Medicago successfully produces VLP vaccine candidate for H7N9 virus | Virology News | Scoop.it

Medicago Inc. (TSX: MDG; OTCQX: MDCGF), a biopharmaceutical company focused on developing highly effective and competitive vaccines based on proprietary manufacturing technologies and Virus-Like Particles (VLPs), today announced that it has successfully produced a new VLP vaccine candidate  for the H7N9 virus that is responsible for the current influenza outbreak in China.


Influenza in birds graphic from Russell Kightley Media

Ed Rybicki's insight:

I keep saying, you gotta go green...and Medicago do, and have for H7N9.

 

Quicker than anyone else, evidently.  Truly impressive for plant production technology!

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Picornavirus interactions with cellular membranes and vesicles

Picornavirus interactions with cellular membranes and vesicles | Virology News | Scoop.it
The entire replication cycle of picornaviruses takes place in the cytosol. Or does it?
Ed Rybicki's insight:

But wait, there's more...nice paper, with some intriguing possibilities raised around how some viruses may have acquired an envelope.

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Is this the reason why RV144 HIV ‘Thai trial’ didn’t protect more participants?

Is this the reason why RV144 HIV ‘Thai trial’ didn’t protect more participants? | Virology News | Scoop.it

The RV144 ‘Thai trial’ of an HIV vaccine candidate resulted in an unprecedented 31% protection rate among participants – a

result that sparked something of a revival in the HIV vaccine field. Despite this encouraging result, the protection rate was still considered to be too low for the vaccine to be useful. Since then, many HIV vaccines have come and gone – with the NIAID’s HVTN 505 trial being the latest casualty in the drive to stem the HIV pandemic. However, researchers at the Duke Human Vaccine Institute have published researched inProceedings of the National Academy of Sciences (May 6th 2013) which pinpoints a previously unknown interaction between IgA and IgG antibodies as the cause of a lack of response to the RV144 vaccine.

 

Killer T-cell graphic by Russell Kightely Media

Ed Rybicki's insight:

VERY interesting, if true: IgA - supposedly the Ab of choice for mucosal surface protection - interfering with IgG, and stopping killer T / NK cells from binding and killing infected cells?

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Scientist: Poultry trade may be spreading deadly bird flu

Scientist: Poultry trade may be spreading deadly bird flu | Virology News | Scoop.it
Poultry workers moving to and from wet markets and farms may be responsible for the spread of the deadly H7N9 virus in China, says a virologist who's working with the World Health Organisation to investigate the outbreak.
Ed Rybicki's insight:

As ever...if people make money from animals, they will trade them even when there is the danger of spreading disease.

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Rising measles outbreaks threaten vaccine-averse

Rising measles outbreaks threaten vaccine-averse | Virology News | Scoop.it

Seven confirmed cases of measles in Toronto, Ontario, so far this year, for a total of 12 in Canada to date, are prompting public health officials to remind doctors that the once-common childhood illness risks establishing a foothold again.

Ed Rybicki's insight:

And why?  Because risk-averse parents aren't vaccinating their children against the things THEY were vaccinated against, which means we're back in the 1950s again as far as morbidity / mortality figures are concerned.

 

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Easy Jump for H5N1 from Bird to Mammal

Easy Jump for H5N1 from Bird to Mammal | Virology News | Scoop.it
Hybrid viruses derived from an H5N1 bird flu strain can infect guinea pigs through the air.
Ed Rybicki's insight:

It is rather concerning that these guys did NOT have to make HA mutations to get their viruses easily transmissible - they just to make reassortants with H5N1 and H1N1pdm viruses.  As could happen in pigs or poultry anywhere both viruses occur....

 
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The highly pathogenic H7N3 avian influenza strain from July 2012 in Mexico acquired an extended cleavage site through recombination with host 28S rRNA

The highly pathogenic H7N3 avian influenza strain from July 2012 in Mexico acquired an extended cleavage site through recombination with host 28S rRNA | Virology News | Scoop.it
A characteristic difference between highly and non-highly pathogenic avian influenza strains is the presence of an extended, often multibasic, cleavage motif insertion in the hemagglutinin protein.

Conclusions

This highly pathogenic H7N3 avian influenza strain acquired a novel extended cleavage site which likely originated from recombination with 28S rRNA from the avian host. Notably, this new virus can infect humans but currently lacks critical host receptor adaptations that would facilitate human to human transmission.

 

Avian influenza virus graphic courtesy of Russell Kightley Media

Ed Rybicki's insight:

This is rather sinister!  Not only can influenza viruses mutate, for antigenic drift, and reassort with one aother for antigenic shift - they can now recombine with HOST sequences to increase pathogenicity!

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Billions of dollars later and still no Aids vaccine - Times LIVE

Billions of dollars later and still no Aids vaccine - Times LIVE | Virology News | Scoop.it
Latest news from South Africa, World, Politics, Entertainment and Lifestyle. The home of The Times and Sunday Times newspaper. (The hunt for an HIV vaccine has gobbled up $8-billion in the past decade with no real results.
Ed Rybicki's insight:

Beause of rampant band-wagon jumping and some ignoring of basic lessons from other lentiviruses...the Ad5 bandwagon was especially noticeable; it will be interesting to see what the new wagon will be, now that this has come to a grinding halt.  Poxviruses, anyone?

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Production of protective bluetongue virus-like particle vaccine in plants

Production of protective bluetongue virus-like particle vaccine in plants | Virology News | Scoop.it

Plant expression systems based on nonreplicating virus-based vectors can be used for the simultaneous expression of multiple genes within the same cell. They therefore have great potential for the production of heteromultimeric protein complexes. This work describes the efficient plant-based production and assembly of Bluetongue virus-like particles (VLPs), requiring the simultaneous expression of four distinct proteins in varying amounts. Such particles have the potential to serve as a safe and effective vaccine against Bluetongue virus (BTV), which causes high mortality rates in ruminants and thus has a severe effect on the livestock trade. Here, VLPs produced and assembled in Nicotiana benthamiana using the cowpea mosaic virus-based HyperTrans (CPMV-HT) and associated pEAQ plant transient expression vector system were shown to elicit a strong antibody response in sheep. Furthermore, they provided protective immunity against a challenge with a South African BTV-8 field isolate.

 

The results show that transient expression can be used to produce immunologically relevant complex heteromultimeric structures in plants in a matter of days. The results have implications beyond the realm of veterinary vaccines and could be applied to the production of VLPs for human use or the coexpression of multiple enzymes for the manipulation of metabolic pathways.

 Generic reovirus-like particle by Russell Kightley Media
Ed Rybicki's insight:

While this has not been subject to the same hype as the FMDV VLPs featured here and all over the media recently, it is at least as big a deal - and yes, we are involved, and yes, we are highly stoked with what we did.

 

Because this is a four-protein virus-like particle, expressed via transient expression in N benthamiana, and assembled in yields high enough to allow purification of particles that were protective in a live virus challenge experiment in sheep.

 

Yes, protective in actual sheep, and competitive with the standard attentuated live virus vaccine - which is a seriously big deal!

 

Plus the electron micrographs of the particles are SO cool.  Congratulations, Eva and team, you have done really, really well.

Frank Sainsbury's comment, May 17, 3:45 AM
Hear, hear!!
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Fears grow over deadly new virus

Fears grow over deadly new virus | Virology News | Scoop.it
The World Health Organization warns that it appears "increasingly" likely that the new coronavirus can be passed between people in close contact.
Ed Rybicki's insight:

Yet ANOTHER damn virus to worry about...B-(  Thanks, Ken Yaw Agyeman-Badu!

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New vaccines needed for pathogens infecting animals and humans: One Health – Dr. Thomas P. Monath

New vaccines needed for pathogens infecting animals and humans: One Health – Dr. Thomas P. Monath | Virology News | Scoop.it
World Vaccine Congress & Expo 2013 

Dr Thomas P. Monath, Adjunct Professor at Harvard School of Public Health gives his presentation on ‘New vaccines needed for pathogens infecting animals and humans: One Health’.

 

Ed Rybicki's insight:

This is a very interesting presentation for a number of reasons - prime among which is the fact that a number of very influential international organisations and funders are taking the notion of "One Health" very seriously.

 

That is, the development of reagents and vaccines that can be used for agents that cause both animal and human diseases, such as avian influenza, Nipah and Hendra and Rift Valley fever viruses, and so on.

 

Great idea - and one we are trying to address with making such things in plants!

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Cassava Viral Disease Spreads at Alarming Rate

Cassava Viral Disease Spreads at Alarming Rate | Virology News | Scoop.it

Scientists say a disease destroying entire crops of cassava has spread out of East Africa into the heart of the continent, is attacking plants as far south as Angola and now threatens to move west into Nigeria, the world's biggest producer of the potato-like root that helps feed 500 million Africans.


Photo: healthy cassava, Ed Rybicki, western Kenya, 1998


Ed Rybicki's insight:

This is a really big deal - and it comes just 15 years or so after another cassava scourge, caused by a recombinant begomovirus, swept out of Uganda.  That one was credited with helping to kill over 20 000 people, due to starvation and assocaited morbidity.  This one - Cassava brown streak virus, or CBSV - is a filamentous ssRNA potyvirus (genus Ipomovirus, family Potyviridae), spread by whiteflies ratehr than the usual potyvirus vector (aphids).

 

Gerhard Pietersen and I noted in 1999 that CBSV was an emerging virus, but not a serious problem (Adv Virus Res, 53, 127-175, 1999).


It has obviously emerged, and is.  Now to deal with it!

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Expression in tobacco and purification of beak and feather disease virus capsid protein fused to elastin-like polypeptides

Expression in tobacco and purification of beak and feather disease virus capsid protein fused to elastin-like polypeptides | Virology News | Scoop.it

Psittacine beak and feather disease, caused by beak and feather disease virus (BFDV), is a threat to endangered psittacine species. There is currently no vaccine against BFDV, which necessitates the development of safe and affordable vaccine candidates. A subunit vaccine based on BFDV capsid protein (CP), the major antigenic determinant, expressed in the inexpensive and highly scalable plant expression system could satisfy these requirements. Full-length CP and a truncated CP (ΔN40 CP) were transiently expressed in tobacco (Nicotiana benthamiana) as fusions to elastin-like polypeptide (ELP). These two proteins were fused to ELPs of different lengths in order to increase expression levels and to provide a simple means of purification. The ELP fusion proteins were purified by inverse transition cycling (ITC) and it was found that a membrane filtration-based ITC method improved the recovery of ΔN40 CP-ELP51 fusion protein relative to a centrifugation-based method.

  
Ed Rybicki's insight:

From *ahem* a little known virology lab somewhere in the far, far South...B-)

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Recombinant Monovalent Llama-Derived Antibody Fragments (VHH) to Rotavirus VP6 Protect Neonatal Gnotobiotic Piglets against Human Rotavirus-Induced Diarrhea

Recombinant Monovalent Llama-Derived Antibody Fragments (VHH) to Rotavirus VP6 Protect Neonatal Gnotobiotic Piglets against Human Rotavirus-Induced Diarrhea | Virology News | Scoop.it

This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.

Ed Rybicki's insight:

Always nice to Scoop a paper from a co-author, in this case Andres Wigdorovitz and friends.  Nice work, too - shows that rotavirus VP6 is a useful recombinant protein target for use as a vaccine, given that llama single-chain Abs specific to it can protect.  But why not make them in plants, Andres??

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Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model

Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model | Virology News | Scoop.it

Infection with influenza virus leads to significant morbidity and mortality. Annual vaccination may prevent subsequent disease by inducing neutralizing antibodies to currently circulating strains in the human population. To escape this antibody response, influenza A viruses undergo continuous genetic variation as they replicate, enabling viruses with advantageous antigenic mutations to spread and cause disease in naïve or previously immune or vaccinated individuals. To date, the 2009 pandemic virus (A(H1N1)pdm09) has not undergone significant antigenic drift, with the result that the vaccine remains well-matched and should provide good protection to A(H1N1)pdm09 circulating viruses. In this study, we induced antigenic drift in an A(H1N1)pdm09 virus in the ferret model. A single amino acid mutation emerged in the dominant surface glycoprotein, hemagglutinin, which had a multifaceted effect, altering both antigenicity and virus receptor specificity. The mutant virus could not be isolated using routine cell culture methods without the virus acquiring additional amino acid changes, yet was fit in vivo. The implications for surveillance of circulating influenza virus are significant as current assays commonly used to assess vaccine mismatch, as well as to produce isolates for vaccine manufacture, are biased against identification of viruses containing only this mutation.

 

Influenza virus graphic by Russell Kightley Media 

Ed Rybicki's insight:

There is a rather disturbing result in this paper: that is, that the mutation in the H1N1 HA that emerged in serial ferret transfers that was responsible for antigenic drift, resulted in a virus that could NOT be cultured by routine methods despite being quite happy in ferrets.  In fact, adapting the virus to culture meant it accumulated MORE mutations, meaning the thing they got out by "current assays" was NOT the same thing that was causing disease.

 

This is worrying for a number of reasons, not least of which is that informed decisions on probable vaccine efficacy are made as a result of such assays - and the vaccines themselves, in some cases.  And if what these decisions are based on is incorrect...?

 

Time for some better science here, people - like next-gen sequencing rather than isolation as a measure of what is causing disease!

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China bird flu scare: H7N9 found to be a deadly mix of four strains

China bird flu scare: H7N9 found to be a deadly mix of four strains | Virology News | Scoop.it
The new H7N9 bird flu strain has been found to be a mixture of genes from four flu strains found in birds even as the first patient with severe symptoms of the deadly disease has made a complete recovery.
Ed Rybicki's insight:

Nasty...just as has been predicted, wild and migratory ducks have been probably responsible for the mixture of viruses that gave rise to the new H7N9.  The rest is down to Chinese farming practices.

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Overview of the Novel Lethal Coronavirus

Overview of the Novel Lethal Coronavirus | Virology News | Scoop.it
CDC Coronavirus: Coronaviruses are common throughout the world. They can infect people and animals. Five different coronaviruses can infect people and make them sick. They usually cause mild to moderate upper-respiratory illness.

 

SARS coronavirus graphic by Russell Kightley Media

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Bitter pill: life-saving HIV drugs fuel crime and addiction in South Africa

Bitter pill: life-saving HIV drugs fuel crime and addiction in South Africa | Virology News | Scoop.it
Three years ago, Sipho Molefe (not his real name) was a normal 16-year-old boy — an athletic, easygoing high schooler who was well liked among his peers in rural South Africa. Today, Sipho is...
Ed Rybicki's insight:

NOT a nice story.  Whoonga and nyaope - made using ARVs, heroin, and who knows what else.  Just sick!

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Detection of specific HPV subtypes responsible for the pathogenesis of genital warts

Detection of specific HPV subtypes responsible for the pathogenesis of genital warts | Virology News | Scoop.it

The aims of the study were to evaluate current strategies used for the monitoring of HPV infection in genital warts and to assess the suitability of laser-capture microdissection (LCM) as a technique to improve the understanding of the natural history of HPV types associated with genital wart lesions.

Methods

DNA and RNA were extracted from whole wart, surface swabs and LCM sections from 23 patients. HPV types present were determined using the Linear Array HPV Genotyping Test (Roche), with HPV DNA viral load and mRNA expression investigated using qPCR and qRT-PCR, respectively.

Results

Results indicated that swabbing the surface of warts does not accurately reflect potential causative HPV types present within a wart lesion, multiple HPV types being present on the surface of the wart that are absent in the lower layers of tissue isolated by LCM. Although it was shown that HPV DNA viral load does not directly correlate with HPV mRNA load, the presence of both DNA and mRNA from a single HPV type suggested a causative role in lesion development in 8/12 (66.6%) of patients analysed, with dual infections seen in 4/12 (33.3%) cases. HPV 6 and HPV 11 were present in more than 90% of the lesions examined.


HPV graphic courtesy of Russell Kightley Media

Ed Rybicki's insight:

Interesting stuff: so, simply swabbing the surface of lesions does NOT give a good indication as to what is causing the lesion - and HPVs 6 and 11 are often present together in condylomas.

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