Viruses, viroids and prions

Give three reasons why viruses are not considered living organisms according to classical criteria (cellular organization, metabolism, and reproduction) and one reason why the debate remains open.

Describe the basic structure of a virus (genome, capsid, and, in some, envelope) and explain the difference between a naked virus and an enveloped virus, with an example of each.

Distinguish between viruses with a DNA genome and those with an RNA genome, and give an example of a disease caused by each type (herpes or smallpox versus flu, measles or COVID-19), indicating what this implies for their variability.

Explain what a bacteriophage is, describe its structure (a head with the genome, a tail and attachment fibres) and indicate what its "prey" is and why each phage infects only certain bacteria.

Describe the lytic cycle and the lysogenic cycle of a bacteriophage, indicating how they differ and what consequence it has for the bacterium when the phage enters latency.

Order and describe the phases of the replication cycle of a virus (adsorption, penetration, replication and synthesis, assembly, release), and indicate at which steps antiviral drugs can act (blocking entry, inhibiting the polymerase or the protease).

What are viroids and what are prions? State which organisms the former infect and give a human or animal disease caused by prions.

A research team is trying to determine the nature of the infectious agent causing a new spongiform encephalopathy. To do so, they subject samples of infectious brain tissue to different treatments before inoculating them into healthy laboratory mice:

• Treatment 1: Exhaustive digestion with DNases and RNases $\rightarrow$ $100\,\%$ of the mice fall ill.

• Treatment 2: Ultraviolet irradiation at lethal doses for nucleic acids $\rightarrow$ $100\,\%$ of the mice fall ill.

• Treatment 3: Autoclaving at $121\text{ }^\circ\text{C}$ for $20\text{ minutes}$ $\rightarrow$ $100\,\%$ of the mice fall ill.

• Treatment 4: Prolonged boiling in sodium hydroxide ($1\text{ M}$) or digestion with harsh proteases $\rightarrow$ No mice fall ill.

• Treatment 5: The intact infectious sample is inoculated into Knock-Out mice in which the $PRNP$ gene has been deleted (they do not express the normal cellular protein $\text{PrP}^\text{C}$) $\rightarrow$ No mice develop the disease or multiply the pathogen.

1. a) Interpret the results of treatments 1, 2, and 4: deduce the biochemical nature of the pathogen and justify why its discovery represented an apparent violation of the central dogma of molecular biology.
2. b) Explain at a structural level (secondary conformation and aggregation) why treatment 3 failed but treatment 4 managed to neutralize infectivity.
3. c) Deduce from treatment 5 the mechanism by which this pathogen manages to "replicate" in a healthy host and explain why mice without the $PRNP$ gene turn out to be immune.

Name three transmission routes of viruses (respiratory, faecal-oral, sexual or blood-borne, via vectors such as mosquitoes) with an example of a disease for each one, and indicate one specific prevention measure for each route.

Flu changes in two ways. Distinguish antigenic drift (annual point mutations) from antigenic shift (recombination between viruses, the origin of pandemics), and discuss why avian and swine flu are monitored as possible sources of new pandemic viruses.

During an outbreak of a novel respiratory virus, a basic reproduction number $R_0 = 2,5$ is estimated.

1. a) Public health authorities consider two alternative scenarios: implementing non-pharmaceutical containment measures (masks and ventilation, which reduce the transmission probability per contact by $40\,\%$) or relying exclusively on a vaccine with an efficacy of $80\,\%$ administered to $60\,\%$ of the population. Quantitatively predict which of the two strategies will independently manage to halt the expansion of the outbreak (making the effective reproduction number $R_t$ less than $1$), justifying your calculations.
2. b) A public official states: "If we manage to vaccinate $50\,\%$ of the population with a $100\,\%$ effective vaccine, the virus will become extinct immediately because half of the population will no longer transmit it". Refute this statement quantitatively and biologically by calculating the resulting value of $R_t$ and describing what will happen in the short term to the epidemic curve.

What is a vaccine and how does it "train" the immune system without causing the disease? Name two types of vaccines (attenuated, inactivated, subunit, messenger RNA) and explain how they differ.

Messenger RNA vaccines were rolled out massively with COVID-19. Explain how they work (a temporary instruction for our cells to manufacture the antigen), what design-speed advantage they offer, and why it is false that they can modify our DNA (where does the mRNA act and what is its half-life?).

You are part of an epidemiological panel that must assess the biological feasibility of eradicating three viral pathogens:

• Virus A (Rabies virus): RNA virus; fatality rate close to $100\,\%$; infects multiple wild mammals (bats, foxes) and domestic mammals; a highly effective inactivated vaccine is available.

• Virus B (Poliovirus type 1): RNA virus; exclusively human reservoir; between $90\,\%$ and $95\,\%$ of infected individuals are completely asymptomatic but shed viable viral particles in feces for weeks; effective oral and inactivated vaccines are available.

• Virus C (Measles virus): RNA virus; exclusively human reservoir; virtually $100\,\%$ of infected individuals develop characteristic full-blown clinical symptoms (fever, rash) with no asymptomatic cases transmitting the disease; $R_0 \approx 12\text{-}18$; an effective attenuated vaccine is available.

1. a) Based on the concept of natural reservoir, justify why Virus A is not biologically eradicable on a global scale, unlike what was achieved with human smallpox.
2. b) Compare the epidemiological difficulties of Virus B versus Virus C: which of the two poses a greater obstacle to the early detection and isolation of transmission chains? Justify your answer.
3. c) Design a non-invasive epidemiological surveillance method that allows detecting the active circulation of Virus B in a city without the need to collect individual clinical samples from the entire population.