Molecular Biology of VIRUS

Question 1

Basic features of a virus

Answer 1

• Cannot produce/ generate Energy
• Obligate intracellular pathogens
• can only reproduce within a host cell
• contain no ribosomes or organelles ⇒ can’t synthesize proteins
• cannot replicate genetic materials
• Do not divide to reproduce, but they replicate
• Metastable structure ( intrinsically unstable)

Question 2

Basic components of a virus

Answer 2

• Genome, RNA or DNA. NOT BOTH
• Capsid (nucleocapside = genome + capsid)
• Envelope. not all viruses have envelopes, i.e naked
• other proteins , may have enzymes, nucleoproteins, matrix proteins

Question 3

Enveloped viruses

Answer 3

have a lipoprotein envelope that is derived from host cell membranes

Question 4

Unenveloped or ‘naked’ viruses

Answer 4

do not have a lipoprotein envelope

Question 5

RNA Viruses

Answer 5

• single stranded (ss); (+) RNA or (-) RNA
• double standed (ds)
• linear or circular

Question 6

DNA virus

Answer 6

• double standed (ds) or single stranded (ss)
• linear or circular

Question 7

1. Entry into the host cell

Answer 7

• Adsorption/attachment : Viral ligands or cellular receptors
• Penetration/entry - pH dependent : Endocytosis (naked and enveloped) or fusion (only enveloped)
• Uncoating to release genome
• (Latent infection – virus stays in ‘sleeping’ state)

Question 8

2. Replication/synthesis/assembly

Answer 8

•Replication of genetic material

• Protein synthesis (enzymes/structural components)

• Viral assembly : Once the viral genome and proteins have been replicated, new virus assembly is usually spontaneous. For many viruses, the viral assembly process occurs at the host plasma membrane.

Question 9

3. Release from host cell

Answer 9

Budding

• usually causes death of cell, but not always ( large amount of budding can cause damage so that the cell has to go into apoptosis)
• enveloped viruses

Lysis

• Causes death of cell
• Naked viruses and some enveloped viruses

Question 10

Genome Replication

Answer 10

• RNA +, RNA ‐, and ds RNA viruses: carry their own replicase/RNA polymerase enzymes that allow for genome replication in the host cytoplasm, don’t need primers
• DNA viruses and retroviruses : may or may not be entirely dependent on host replication enzymes (if not, they carry their own enzymes), replication occurs in host nucleus

Question 11

RNA (+)

Answer 11

• Host cytoplasm
• Immediate translation, no need for transcription
• Replication requires RNA‐dependent RNA polymerase

Question 12

RNA (-)

Answer 12

• Host cytoplasm
• Transcription must occur first before translation
• Requires RNA‐dependent RNA polymerase for transcription and replication

Question 13

DS RNA

Answer 13

• Host cytoplasm
• Transcription must occur first before translation
• Requires RNA‐dependent RNA polymerase for transcription and replication

Question 14

DS DNA virus

Answer 14

• Host Nucleus
• Transcription must occur before translation
• transcription and replication may need host enzymes ; if they depend on viral enzymes ⇒ can target these with drugs
• Replication and transcription of DNA viruses occurs in the nucleus, the viral DNA may or may not into the host DNA – this is virus‐type specific (most don’t). DNA viruses may use some or all of the host DNA replication and transcription machinery/enzymes to generate new virions.

Question 15

Retro Virus

Answer 15

• Host nucleus
• After reverse transcription, viral DNA must integrate into host genome
• Transcription must occur before translation
• Virus is partially dependent on host enzymes
• Ex. HIV virus

Question 16

HIV

Answer 16

• Entry into cell depends on binding of viral gp120 to host cell CD4 receptors and host CCR5 or CXCR4 corecptors.
• HIV = enveloped virus so it leaves host cell via budding.
• Protease helps viral maturation of the released virus by cleaving large inactive polyproteins into several active proteins that are needed for viral function/ the infection of other cells

Note that CD4 is a receptor expressed by immune system cells and this is the reason why HIV causes immune deficiency.

Question 17

Drug classes that prevent entry of HIV virus into cells

Answer 17

• Fusion Inhibitors: Enfuvirtide
• MOA : it prevents the HIV virus from entering the host cell by blocking gp41

Question 18

Drug classes to prevent synthesis of ds HIV DNA

Answer 18

• NNRTI’s and NRTI’s
• they terminate the DNA synthesis through chain termination

Question 19

Drug classes to prevent integration of HIV virus into the host genome

Answer 19

• Integrase Inhibitor, eg. Elvitegravir
• It prevents the DNA virus to integrate into the host’s chromosomes.

Question 20

Drug classes to prevent generation of a mature virion

Answer 20

• Protease Inhibitor, eg. Ritonavir
• Inhibits the protease from cleaving the polypeptide into mature viral proteins

Question 21

NRTI’s

Answer 21

mimic true deoxynucleotides and incorporate into the elongating DNA chain. Because they lack a 3’ OH group ( sticky end), chain elongation is terminated

Question 22

NNRTI’s

Answer 22

bind to reverse transcriptase away from the active site, causing a conformational change in the enzyme rendering in active