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hemorrhagic fever

TWiV 985: Bambi’s revenge

19 February 2023 by Vincent Racaniello

TWiV reviews an outbreak of Marburg hemorrhagic fever in Equatorial Guinea, wild poliovirus type 3 shedding from a laboratory in the Netherlands, and white-tailed deer as a reservoir for previous SARS-CoV-2 variants of concern.

Hosts: Vincent Racaniello, Dickson Despommier, and Rich Condit

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Show notes at microbe.tv/twiv

Filed Under: This Week in Virology Tagged With: coronavirus, COVID-19, hemorrhagic fever, IPV, marburg virus, pandemic, poliovirus, poliovirus essential facility, SARS-CoV-2, variant of concern, viral, virology, virus, viruses, white-tailed deer

More filoviruses in bats

31 January 2019 by Vincent Racaniello

Ebola dishThe family of viruses known as the Filoviridae (filo, from the Latin for thread) is well known for the ebolaviruses, which cause the hemorrhagic disease that regularly erupts in Africa. As Earth’s virome is slowly revealed, other filoviruses are discovered.

[Read more…] about More filoviruses in bats

Filed Under: Basic virology, Information Tagged With: ebolavirus, filovirus, hemorrhagic fever, Mengla virus, minigenote, spillover, viral, virology, virus, viruses

Lassa virus origin and evolution

13 August 2015 by Vincent Racaniello

arenavirusI have a soft spot in my heart for Lassa virus: a non-fictional account of its discovery in Africa in 1969 inspired me to become a virologist. Hence papers on this virus always catch my attention, such as one describing its origin and evolution.

Lassa virus, a member of the Arenavirus family, is very different from Ebolavirus (a filovirus), but both are zoonotic pathogens that may cause hemorrhagic fever. It is responsible for tens of thousands of hospitalizations, and thousands of deaths each year, mainly in Sierra Leone, Guinea, Liberia, and Nigeria. Most human Lassa virus outbreaks are caused by multiple exposures to urine or feces from the multimammate mouse, Mastomys natalensis, which is the reservoir of the virus in nature. In contrast, outbreaks of Ebolavirus infection typically originate with a crossover from an animal reservoir, followed by human to human transmission. Despite being studied for nearly 50 years, until recently the nucleotide sequences of only 12 Lassa virus genomes had been determined.

To remedy this lack of Lassa virus genome information, the authors collected clinical samples from patients in Sierra Leone and Nigeria between 2008 and 2013. From these and other sources they determined the sequences of 183 Lassa virus genomes from humans, 11 viral genomes from M. natalensis, and two viral genomes from laboratory stocks. All the data are publicly available at NCBI. Analysis of the data lead to the following conclusions:

  • Lassa virus forms four clades, three in Nigeria and one in Sierra Leona/Liberia (members of a clade evolved from a common ancestor).
  • Most Lassa virus infections are a consequence of multiple, independent transmissions from the rodent reservoir.
  • Modern-day Lassa virus  strains probably originated at least 1,000 years ago in Nigeria, then spread to Sierra Leone as recently as 150 years ago. The lineage is most likely much older, but how much cannot be calculated from the data.
  • The genetic diversity of Lassa virus in individual hosts is an order of magnitude greater than the diversity of Ebolavirus. Furthermore, Lassa virus diversity in the rodent host is greater than in humans, likely a consequence of the longer, persistent infections that take place in the mouse.
  • The gene encoding the Lassa virus glycoprotein is subject to high selection in hosts, leading to variants that interfere with antibody binding.
  • Genetic variants that arise in one rodent are not transmitted to another.

Perhaps the most important result from this work is the establishment of laboratories in Sierra Leone and Nigeria that can safely collect and process samples from patients infected with Lassa virus, a BSL-4 pathogen.

Filed Under: Basic virology, Information Tagged With: arenavirus, ebolavirus, evolution, genome sequence, hemorrhagic fever, Lassa virus, Mastomys natalensis, nigeria, reservoir, Sierra Leone, viral, virology, virus, zoonosis

TWiV 341: Ebolavirus experiences

15 June 2015 by Vincent Racaniello

On episode #341 of the science show This Week in Virology, Vincent returns to the University of Glasgow MRC-Center for Virus Research and speaks with Emma, Gillian, and Adam about their ebolavirus experiences: caring for an infected patient, working in an Ebola treatment center in Sierra Leone, and making epidemiological predictions about the outbreak in west Africa.

You can find TWiV #341 at www.microbe.tv/twiv.

Filed Under: This Week in Virology Tagged With: Centre for Virus Research, Ebola patient, Ebola treatment center, ebolavirus, epidemiology, ETC, hemorrhagic fever, outbreak, Sierra Leone, University of Glasgow, vaccine, viral, virology, virus

Ebolavirus will not become a respiratory pathogen

21 February 2015 by Vincent Racaniello

sneezeAn otherwise balanced review of selected aspects of Ebolavirus transmission falls apart when the authors hypothesize that ‘Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread.’

The idea that Ebolavirus might become transmitted by the respiratory route was suggested last year by Michael Osterholm in a Times OpEd. That idea was widely criticized by many virologists, including this writer.  Now he has recruited 20 other authors, including Ebola virologists, in an attempt to lend legitimacy to his hypothesis. Unfortunately the new article adds no new evidence to support this view.

In the last section of the review article the authors admit that they have no evidence for respiratory transmission of Ebolavirus:

It is very likely that at least some degree of Ebola virus transmission currently occurs via infectious aerosols generated from the gastrointestinal tract, the respiratory tract, or medical procedures, although this has been difficult to definitively demonstrate or rule out, since those exposed to infectious aerosols also are most likely to be in close proximity to and in direct contact with an infected case.

It is possible that some short-distance transmission of Ebolavirus occurs through the air. But claiming that it is ‘very likely’ to be taking place is an overstatement considering the lack of evidence. As might be expected, ‘very likely’ is exactly the phrase picked up by the Washington Post.

I find the lack of critical thinking in the following paragraph even more disturbing:

To date, investigators have not identified respiratory spread (either via large droplets or small-particle aerosols) of Ebola viruses among humans. This could be because such transmission does not occur or because such transmission has not been recognized, since the number of studies that have carefully examined transmission patterns is small. Despite the lack of supportive epidemiological data, a key additional question to ask is whether primary pulmonary infections and respiratory transmission of Ebola viruses could be a potential scenario for the future.

Why is the possibility of respiratory transmission of Ebolaviruses a ‘key additional question’ when there has been no evidence for it to date? To make matters worse, the authors have now moved from short-range transmission of the virus by droplets, to full-blown respiratory aerosol transmission.

The authors present a list of reasons why they think Ebolavirus could go airborne, including: isolation of Ebolaviruses from saliva; presence of viral particles in pulmonary alveoli on human autopsies; and cough, which can generate aerosols, can be a symptom of Ebolavirus disease. The authors conclude that because of these properties, the virus would not have to change very much to be transmitted by aerosols.

I would conclude the opposite from this list of what Ebolavirus can do: there is clearly a substantial block to respiratory transmission that the virus cannot overcome. Perhaps the virus is not stable enough in respiratory aerosols, or there are not enough infectious viruses in aerosols to transmit infection from human to human. Overcoming these blocks might simply not be biologically possible for Ebolavirus. A thoughtful discussion of these issues is glaringly absent in the review.

The conclusion that Ebolavirus is  ‘close’ to becoming a full-blown respiratory pathogen reveals how little we understand about the genetic requirements for virus transmission. In fact the authors cannot have any idea how ‘close’ Ebolavirus is to spreading long distances through the air.

It is always difficult to predict what viruses will or will not do. Instead, virologists observe what viruses have done in the past, and use that information to guide their thinking. If we ask the simple question, has any human virus ever changed its mode of transmission, the answer is no. We have been studying viruses for over 100 years, and we’ve never seen a human virus change the way it is transmitted. There is no evidence to believe that Ebolavirus is any different.

Viruses are masters of evolution, but apparently one item lacking from their repertoire is the ability to change the way that they are transmitted.

Such unfounded speculation would largely be ignored if the paper were read only by microbiologists. But Ebolavirus is always news and even speculation does not go unnoticed. The Washington Post seems to think that this review article is a big deal. Here is their headline: Limited airborne transmission of Ebola is ‘very likely’ new analysis says.

Gary Kobinger, one of the authors, told the Washington Post that ‘we hope that this review will stimulate interest and motivate more support and more scientists to join in and help address gaps in our knowledge on transmission of Ebola’. Such hope is unrealistic, because few can work on this virus, which requires the highest levels of biological containment, a BSL-4 laboratory.

I wonder if Osterholm endorses Kobinger’s hopes. After all, he opposed studies of influenza virus transmission in ferrets, claiming that they are too dangerous. And the current moratorium on research that would help us understand aerosol transmission of influenza viruses is a direct result of objections by Osterholm and his colleagues about this type of work. The genetic experiments that are clearly needed to understand the limitations of Ebolavirus transmission would never be permitted, at least not with United States research dollars.

The gaps in our understanding of virus transmission are considerable. If virologists are not able to carry out the necessary experiments to fill these gaps, all we will have is rampant and unproductive speculation.

Filed Under: Basic virology, Commentary, Information Tagged With: aerosol, droplets, Ebola, ebolavirus, hemorrhagic fever, Michael Osterholm, mutation, respiratory transmission, transmission, viral, virology, virus

TWiV 314: Einstein goes viral

7 December 2014 by Vincent Racaniello

On episode #314 of the science show This Week in Virology, Vincent travels to Albert Einstein College of Medicine where he speaks with Kartik, Ganjam, and Margaret about their work on Ebolavirus entry, a tumor suppressor that binds the HIV-1 integrase, and the entry of togaviruses and flaviviruses into cells.

You can find TWiV #314 at www.microbe.tv/twiv.

Filed Under: This Week in Virology Tagged With: CDC protein, checkpoint, cholesterol, ebola virus, Ebolaviruses, endosome, hemorrhagic fever, HIV-1, INI1, integrase, lysosome, membrane fusion, monoclonal antibody, NPC1, rhabdoid tumor, tumor suppressor, viral, virology, virus, virus entry

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