Molecular Biology of VIRUS Flashcards
Basic features of a virus
- 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)
Basic components of a virus
- 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
Enveloped viruses
have a lipoprotein envelope that is derived from host cell membranes
Unenveloped or ‘naked’ viruses
do not have a lipoprotein envelope
RNA Viruses
- single stranded (ss); (+) RNA or (-) RNA
- double standed (ds)
- linear or circular
DNA virus
- double standed (ds) or single stranded (ss)
- linear or circular
- Entry into the host cell
- 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)
- Replication/synthesis/assembly
•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.
- Release from host cell
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
Genome Replication
- 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
RNA (+)
- Host cytoplasm
- Immediate translation, no need for transcription
- Replication requires RNA‐dependent RNA polymerase
RNA (-)
- Host cytoplasm
- Transcription must occur first before translation
- Requires RNA‐dependent RNA polymerase for transcription and replication
DS RNA
- Host cytoplasm
- Transcription must occur first before translation
- Requires RNA‐dependent RNA polymerase for transcription and replication
DS DNA virus
- 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.
Retro Virus
- 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
HIV
- 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.
Drug classes that prevent entry of HIV virus into cells
- Fusion Inhibitors: Enfuvirtide
- MOA : it prevents the HIV virus from entering the host cell by blocking gp41
Drug classes to prevent synthesis of ds HIV DNA
- NNRTI’s and NRTI’s
- they terminate the DNA synthesis through chain termination
Drug classes to prevent integration of HIV virus into the host genome
- Integrase Inhibitor, eg. Elvitegravir
- It prevents the DNA virus to integrate into the host’s chromosomes.
Drug classes to prevent generation of a mature virion
- Protease Inhibitor, eg. Ritonavir
- Inhibits the protease from cleaving the polypeptide into mature viral proteins
NRTI’s
mimic true deoxynucleotides and incorporate into the elongating DNA chain. Because they lack a 3’ OH group ( sticky end), chain elongation is terminated
NNRTI’s
bind to reverse transcriptase away from the active site, causing a conformational change in the enzyme rendering in active
