# Presentation: 746122

## Viral Voyages

- Structural Biologist Mavis Agbandje-McKenna:
*Understanding Viruses*

## Mavis Agbandje-McKennaCloses in on Viruses

*Structural biologist Agbandje-McKenna wants to solve the mysteries of how viruses hop from one host to another.*

*Viruses*
- Range from harmless to deadly
- Can change from harmless to deadly
- Need carbohydrates to enter cells

*Question:*
- What is another name for carbohydrates?

## Answer: Glycans

- Carbohydrates: essential for many biological processes

- Cell communication

- Inflammation

- Pregnancy

## Gripping Glycans

- Most cells have carbohydrates (glycans) on their outer surfaces
- Influenza A virus infects cells by attaching to glycans on host cells

- Influenza A virus infects a host cell

- Neuraminidase

- Hemagglutinin

- Glycan chain of   host cell

- Protein

- Membrane of host cell

## Visualizing Viruses

- Outer layer (_capsid protein_) of MVM resembles 20-sided soccer ball
- MVM capsid protein contains cavity it uses to recognize and bind specific glycans

- 3-dimensional crystal structure showing surface of usually mild strain of minute virus of mice (MVMp)

## Unraveling Viral Mysteries Step-By-Step

**Make an observation**

**Formulate a research question**

**Formulate hypothesis**

**Investigate**

**Review known facts**

**Draw conclusions from discoveries**

## Solving Viral Mystery #1

**Observation:** MVMp-infected mice are suddenly dying.

**Research question:** What made MVMp become deadly?

**Hypothesis:** Genetic change created mutant capsid protein.

**Investigation:** Decode genetic sequence of deadly MVMp and compare with normal MVMp genetic sequence.

**Known facts:** Both strains of MVM are molecularly similar but have alterations in 14 of 587 amino acids that make up the virus’ protective capsid protein shell.

**Discoveries:** 3 mutations, each causing a unique change in 1 amino acid in the capsid protein.

## Solving Viral Mystery #2

**Observation:** Mutated MVMp has 1 amino acid that differs from normal MVMp.

**Research question: **What makes the mutation deadly?

**Hypothesis:** Change is located in critical region of capsid shell.

**Investigation:** Develop 3-D structure of MVM to identify locations of 3 mutant amino acids.

**Known facts:** MVM capsid protein contains a cavity it uses to recognize and bind specific glycans so that the virus can enter and infect cells.

**Discoveries:** At least 2 changed amino acids sit inside the capsid shell cavity.

## Poultry, People, and a Possible Pandemic

*Poultry, People, and a Possible Pandemic*

- H5N1
- Largest and most lethal epidemic on record
- Migratory birds
- Spread virus
- Infect domestic birds
- Lethal strain of bird flu
- Constantly changing genetically
- Humans who handle infected birds can get virus

- What could happen if . . .

- H5N1 mutates into a strain that “jumps” the species barrier

- H5N1 is carried across continents by migratory birds

**?**

- H5N1 mutates in more ways in response to different environments

**?**

- H5N1 mutates into a strain that spreads more easily between people

## Glycobiology and Pandemics

- What is glycobiology?

- How might glycobiology help prevent a pandemic flu?

- What is the name of the technique shown in the picture?

## Research Applications

- In what ways might Agbandje-McKenna’s research about how viruses infect cells be applied to help patients with cancer?