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About viruses and viral disease

vaccinia

Should we be worried about monkeypox?

7 July 2022 by Gertrud U. Rey

by Gertrud U. Rey

The prevalence of monkeypox cases is continuing to increase around the world, with 7,243 total confirmed global cases as of today. Although this sounds awfully familiar, monkeypox virus is highly unlikely to cause a pandemic like the one we are presently experiencing, for at least two reasons: 1) monkeypox virus is not transmitted as easily as SARS-CoV-2, and 2) we have all the tools needed for quelling local outbreaks, thus hopefully preventing further community spread.

Because monkeypox has been endemic to Central and West Africa for several decades, scientists have had ample time to develop a thorough understanding of the virus and its associated disease. Monkeypox virus belongs to the Poxviridae, a family of viruses that also includes cowpox virus, variola virus (which causes smallpox), and vaccinia virus (the source of the modern smallpox vaccine). The name “monkeypox” resulted from the fact that the virus infects primates and was initially isolated from a laboratory monkey. However, it is actually thought to also circulate in rodents, which occasionally come into contact with humans, who can then further spread it to other humans.

Human-to-human transmission of monkeypox virus is far less efficient than that of SARS-CoV-2, which is commonly spread in the absence of symptoms, whereas monkeypox virus is only thought to be transmitted while an infected person is symptomatic. In addition, SARS-CoV-2 is readily spread when an infected person breathes, sneezes, or coughs around other people. In contrast, monkeypox virus is only transmitted by direct contact with lesion material or inhalation of respiratory droplets during prolonged face-to-face interaction with an infected person. Recent news reports have highlighted clusters of infections among men who have sex with men, leading some to infer that monkeypox is a sexually-transmitted disease. However, there is no evidence to suggest that the virus is present in sexual bodily fluids, therefore, it is not considered to be a sexually-transmitted pathogen. The high incidence of infections in the gay community could be explained by transmission through very close contact, which, by definition, includes sex.

The incubation period for monkeypox virus can range from 5 to 21 days, with an average of one week between infection and onset of symptoms. Initial symptoms usually include fever, swollen lymph nodes, headache, and muscle aches; and these symptoms are followed by a distinctive skin rash consisting of clear fluid-filled vesicles. The vesicles eventually fill with pus and ultimately crust over to give way to a new layer of healthy skin. Early symptoms are similar to those of chickenpox, which is caused by varicella-zoster virus (a herpesvirus, unrelated to poxviruses). However, unlike chickenpox lesions, which can individually exist in different stages of development throughout the course of infection, monkeypox lesions typically appear, progress, and disappear together.

Should the need arise, there are at least two licensed smallpox-specific vaccines that can also prevent monkeypox. ACAM2000 is a replication-competent live-attenuated vaccinia virus developed by Sanofi Pasteur Biologics Co. This vaccine is administered with a traditional bifurcated needle, and although very effective, it is associated with pretty severe side effects, including sore arm, fever, body aches, and occasional myocarditis. MVA-BN (marketed as “Jynneos” in the US) is a highly attenuated replication-incompetent vaccinia virus produced by Bavarian Nordic. MVA-BN/Jynneos is delivered by injection under the skin, is much better tolerated than ACAM2000, and is approved to be used as a monkeypox-specific vaccine. Fortunately, because of the long incubation period, it is possible to be vaccinated shortly after an exposure to monkeypox virus and still be protected from monkeypox disease.

It is unclear how long either of the available vaccines protect a person from disease, and whether individuals who were immunized against smallpox decades ago are protected from monkeypox today. Routine global smallpox vaccination ended in the late 1970s, so it is likely that the current outbreaks are fueled by non-immune people who were born since then, and/or by vaccinated individuals whose immunity has waned. However, even if infections continue to increase in number, it is unlikely that everybody in the general population would need to be vaccinated. Instead, proactively administering the vaccine to contacts and contacts of contacts of an infected person in a strategy termed “ring vaccination” would probably be sufficient to stop spread. That is, the vaccine would be administered in an area in a ring around the outbreak.

There are also several FDA-approved antiviral drugs that could be effective against monkeypox virus infection. Tecovirimat, which can be taken orally, prevents release of newly formed viral particles from infected cells, thus potentially blocking transmission of monkeypox virus. Cidofovir (administered by infusion into the vein) and its derivative brincidofovir (taken orally), disrupt replication of smallpox virus and could thus also be used for treating monkeypox virus infection.  

Considering all these factors, the average person is at low risk of becoming infected with monkeypox virus. Nevertheless, the World Health Organization has declared that there is no room for complacency and is urging governments to take some coordinated action to stop the spread of the virus. Because we have the tools to deal with monkeypox outbreaks and have hopefully learned from the disorganized manner in which the present pandemic was handled initially, a federal preparedness response should be implemented as soon as possible.

[The monkeypox outbreak was previously covered at least on Infectious Disease Puscast episodes 3 and 4; TWiV 902, TWiV 915; and TWiV Special Monkeypox Clinical Update with Dr. Daniel Griffin.]

Filed Under: Basic virology, Gertrud Rey, Information Tagged With: acam2000, antiviral drug, bifurcated needle, bodily fluids, brincidofovir, cidofovir, fluid-filled vesicles, Jynneos, lesion, men who have sex with men, monkeypox, MVA-BN, Poxviridae, ring vaccination, sexually transmitted disease, smallpox, symptoms, tecovirimat, transmission, vaccine, vaccinia, variola

TWiV 130: Rhino tracking, wrestling pox, and HCV in the crosshairs

24 April 2011 by Vincent Racaniello

organ culture hrv cHosts: Vincent Racaniello, Alan Dove, and Rich Condit

Vincent, Alan, and Rich discuss growth in culture of newly identified rhinovirus C, vaccinia transmission among wrestlers and martial artists, and results of phase III clinical trial of boceprevir, a new inhibitor of hepatitis C virus replication.

[powerpress url=”http://traffic.libsyn.com/twiv/TWiV130.mp3″]

Click the arrow above to play, or right-click to download TWiV #130 (45 MB .mp3, 93 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

  • Growth of newly identified rhinovirus C (Nature Medicine)
  • Global distribution of rhinovirus C (EID)
  • Vaccinia transmission among wrestlers (EID)
  • Vaccine transmission in a martial arts gym (EID)
  • Boceprevir for untreated HCV infection (NEJM)
  • Boceprevir for previously treated HCV infection (NEJM)
  • HCV antiviral pipeline
  • The good viruses (Nat Rev Micro)
  • TWiV on Facebook
  • Letters read on TWiV 130

Weekly Science Picks

Rich – Rock-paper-scissors vs computer (thanks, Megan!)
Alan –
WebCite
Vincent – Edward Jenner Museum (EID)

Listener Pick of the Week

Derek Tolly  – A Paralyzing Fear: The Story of Polio in America (IMDb)

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Filed Under: This Week in Virology Tagged With: antiviral, boceprevir, HCV, hepatitis C virus, infectious DNA, organ culture, rhinovirus c, smallpox, vaccinia, viral, virology, virus

TWiV 118: The virus always rings twice

30 January 2011 by Vincent Racaniello

Hosts: Vincent Racaniello, Alan Dove, and Rich Condit

On episode #118 of the podcast This Week in Virology, Vincent, Alan, and Rich answer listener questions about vaccinia virus, fungal viruses, synthetic viruses, influenza vaccine, HeLa cells, multiplicity of infection, and much more.

[powerpress url=”http://traffic.libsyn.com/twiv/TWiV118.mp3″]

Click the arrow above to play, or right-click to download TWiV #118 (68 MB .mp3, 94  minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

  • Distribution of glycoproteins on virion surface (paper 1, paper 2) – thanks, Conor!
  • Susceptibility of cancer cell lines to tanapox (thanks, Cheryl!)
  • Poxvirus family tree
  • Sugar, the bitter truth (YouTube) – thanks, Mary!
  • BBC podcast: Artificial life (thanks, Sam!)
  • Arthritis and influenza at CDC
  • Multiplicity of infection at virology blog
  • Virus-like particle vaccines (thanks, Sheldon!)
  • TWiV on Facebook
  • Letters read on TWiV 118

Weekly Science Picks

Alan – What you need to know about infectious disease
Rich – Bad Project (YouTube)
Vincent – Federal research center will help develop medicines

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Filed Under: This Week in Virology Tagged With: arsenic, entropy, fungal virus, HeLa cells, influenza vaccine, moi, synthetic virus, vaccinia, viral, virology, virus

Rich Condit reminisces

28 December 2010 by Vincent Racaniello

infectious polio rnaOn my recent trip to record TWiV #111 at Florida Gulf Coast University, I visited Rich Condit in Gainesville. There he told me a story about how the bacteriophage T7 polymerase/promoter system was developed. It’s an interesting tale that demonstrates how important scientific advances often have convoluted roots. You can watch the video below or download a high-definition (720p) version (585 MB .mov).

The combination of bacteriophage T7 RNA polymerase and its cognate promoter sequence allows the production of specific RNAs either in vitro or in cells. In many laboratories this system is used to synthesize infectious viral RNA from cloned DNAs. In the example shown, a DNA copy of of the poliovirus RNA genome has been cloned into a bacterial plasmid. The promoter sequence for T7 RNA polymerase is inserted at the 5′-end of the viral sequence (not shown). When placed within any double-stranded DNA, this 19 nucleotide promoter sequence (TAATAGGACTCACTATAGG) will lead to the production of RNA. The plasmid is incubated with purified T7 RNA polymerase (commercially available) and ATP, GTP, UTP and CTP, and the viral RNAs that are produced are then transfected into cells. A viral replication cycle begins, resulting in the production of infectious virus particles.

As described by Rich in the video below, this expression system was conceived by Ed Niles and brought to practice by Bernard Moss. The first paper published described the insertion of the gene encoding T7 RNA polymerase into the genome of vaccinia virus. When cells are infected with the recombinant virus, they produce T7 RNA polymerase. To express a protein using this system, a gene is cloned into a plasmid next to the T7 RNA polymerase promoter. When this plasmid is introduced into cells producing T7 RNA polymerase, RNAs are made which are then translated into protein.

This method was subsequently modified by Wimmer and colleagues to synthesize infectious poliovirus RNA in vitro.

Werf, S. (1986). Synthesis of Infectious Poliovirus RNA by Purified T7 RNA Polymerase Proceedings of the National Academy of Sciences, 83 (8), 2330-2334 DOI: 10.1073/pnas.83.8.2330

Fuerst, T. (1986). Eukaryotic Transient-Expression System Based on Recombinant Vaccinia Virus that Synthesizes Bacteriophage T7 RNA Polymerase Proceedings of the National Academy of Sciences, 83 (21), 8122-8126 DOI: 10.1073/pnas.83.21.8122

Filed Under: Basic virology, Information Tagged With: bacteriophage, condit, poliovirus, promoter, t7 polymerase, vaccinia, viral, virology, virus

TWiV 112: Creating a killer poxvirus

19 December 2010 by Vincent Racaniello

dickson despommierHosts: Vincent Racaniello, Alan Dove, and Rich Condit

On episode #112 of the podcast This Week in Virology, Vincent, Alan, and Rich review the making of a virulent poxvirus by insertion of the gene encoding IL-4, and severe 2009 H1N1 influenza due to pathogenic immune complexes.

[powerpress url=”http://traffic.libsyn.com/twiv/TWiV112.mp3″]

Click the arrow above to play, or right-click to download TWiV #112(71 MB .mp3, 98 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with Stitcher Radio.

Links for this episode:

  • Expression of IL-4 makes a killer poxvirus
  • Additional studies on poxvirus-IL-4 recombinants
  • Creation of killer poxvirus could have been predicted
  • Interleukin regulation of Th responses
  • Severe pandemic H1N1 disease due to immune complexes
  • Unusually high influenza mortality in 18-65 years old
  • The complement system
  • TWiV on Facebook
  • Letters read on TWiV 112

Weekly Science Picks

Rich – The Scientist’s Top 10 Innovations 2010
Alan – Avian Vocalizations Center
Vincent – Microbial soap from Cleaner Science (thanks, Nadia!)

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Filed Under: This Week in Virology Tagged With: bioterrorism, complement, ectromelia, H1N1, influenza, pandemic, podcast. twiv, poxvirus, smallpox, vaccinia, viral, virology, virus

TWiV 95: Does a virus shift in the woods?

15 August 2010 by Vincent Racaniello

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, and Rich Condit

On episode #95 of the podcast This Week in Virology, Vincent, Dickson, Alan, and Rich consider the end of the influenza H1N1 pandemic, dengue in Florida, vaccinia virus infection in Brazilian monkeys, and viruses in the faecal microbiota.

[powerpress url=”http://traffic.libsyn.com/twiv/TWiV095.mp3″]

Click the arrow above to play, or right-click to download TWiV #95 (68 MB .mp3, 94 minutes)

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with Stitcher Radio.

Links for this episode:

  • WHO declares end of influenza H1N1 pandemic
  • CDC’s FluView
  • WHO global monitoring of influenza
  • Locally acquired dengue in Key West, Florida (MMWR)
  • CDC page on dengue
  • Vaccinia virus infection in monkeys of the Brazilian Amazon
  • Dam site where animals were collected for vaccinia study (Google maps)
  • Rich’s article: Whence feral vaccinia?
  • Viruses in the faecal microbiota of monozygotic twins and their Mothers (Nature)
  • New Yorker article The Treatment (thanks, Jim!)
  • Letters read on TWiV 95

Weekly Science Picks

Alan – Families Fighting Flu
Rich –
Food, Inc.
Dickson –  Fuel
Vincent – MIT Open Courseware
Michael –  Waiting for Superman and Can Science Feed the World? (Nature)

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Filed Under: This Week in Virology Tagged With: bacteriophage, Brazil, Dengue, fecal, H1N1, influenza, microbiota, pandemic, podcast, swine flu, vaccinia, viral, virology, virus

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by Vincent Racaniello

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