Viral pathogens classification, biology, diseases 1

Question 1

Define what a virus is

Answer 1

A virus is a microscopic infectious agent that replicates only inside the living cell of an organism

Structure:

• Viruses are aomposed of a nucleic acid genome enclosed in a protein coat known as a capsid
• Some viruses also have an outer lipid envelop derived from the host cell membrane
• The capsid is made up of protein subunits called capsomeres
• Inside, the virus carries its genetic material, either DNA or RNA

Size:

• viruses are much smaller than bacteria, usually 20-300nm in diameter
• Can’t be seen under a light microscope; requires an electron microscope

Reproduction:

• Viruses cannot reproduce by themselves
• They must enter a host cell and use the host’s cellular machinery to replicate their genetic material and produce new virus particles (virions)
• results in the death of the host cell, releasing the newly formed virions to infect more cell

Host Range:

• A set of species that it can infect

Question 2

Compare a virus to bacteria and prions

Answer 2

Structure:

Viruses:

• Acellular entities consisting of a nucleic acid (DNA or RNA) surrounded by a protein coat called a capsid
• Some also have a lipid envelope from host cell membrane
• Lack cellular components and are unable to carry out metabolic processes independently

Bacteria:

• unicellular microorganisms with a simple cellular organisation
• have both DNA and RNA in their cells and can carry out their metabolic processes
• surrounded by a cell wall which provides them with shape and structural integrity

Prions:

• even simpler than viruses, they are the misfolded forms of normal proteins found in the cells

Replication:

Viruses:

• Obligate intracellular parasites, meaning they need to invade a host cell to replicate
• virus uses the host’s cellular machinery to replicate its nucleic acid and synthesise new virus particles

Bacteria:

• capable of independent reproduction by binary fission, a type of asexual reproduction where one cell divides into two identical cells

Prions:

• They don’t reproduce in a traditional sense. They propagate by inducing the misfolding of normal proteins into the prion form

Disease-causing mechanisms:

Viruses:

• by invading host cells and hijacking their machinery for their replication, often killing the cells in the process
• the immune response to viral infection can also contribute to disease symptoms such as inflammation

Bacteria:

• releasing toxins that harm host tissues, invading and destroying host tissues, and eliciting a damaging immune response (inflammation)

Prions:

• by inducing the misfolding of normal cellular proteins, leading to the accumulation of these misfolded proteins in tissues, particularly the brain
• This accumulation disrupts cell function and leads to cell death, resulting in neurodegenerative diseases like Creutzfeldt-Jakob disease

Treatment:

Viruses:

• difficult to treat due to the intracellular lifestyle of viruses
• Antiviral drugs can inhibit the replication of viruses but they often have limited effectiveness and may come with side effects
• Vaccines are effective preventive measure

Bacteria:

• antibiotics that inhibit vital bacterial processes

Prions:

• Currently untreatable
• Focus is on prevention by controlling the exposure to prion-contaminated tissues

Question 3

Define essential features of HIV

Answer 3

Structure and Composition:

• an enveloped virus, meaning it has a lipid bilayer membrane derived from the host cell
• Embedded in this envelope are glycoproteins (gp120 and gp41) necessary for the virus’s attachment and entry into host cells
• Inside the envelope, the virus has a capsid made of protein p24 which encloses two single-stranded RNA genomes and three essential replication enzymes: reverse transcriptase, integrase, and protease

Replication Cycle:

• HIV enters a host cell by binding to the CD4 receptor and either the CCR5 or CXCR4 co-receptor on the surface of the cell (usually a CD4+ T-helper cell)
• After fusion and entry, the viral RNA is reverse-transcribed into DNA by the reverse transcriptase
• The resulting DNA is integrated into the host cell’s genome using integrase
• This allows the virus to use the host’s own replication machinery to produce viral proteins and RNA, which are then assembled into new viral particles, released, and matured by the action of the viral protease

Disease Progression:

• HIV infection typically progresses in three stages: acute infection, clinical latency, and AIDS
• During the acute infection stage, a person may experience a brief, flu-like illness
• The clinical latency stage last years, and while HIV is still replicating, it does so at lower levels, and the person may not experience any symptoms
• When the immune system becomes severely damaged and CD4+ T cell counts drop below a certain level, the person progresses to AIDS and can develop severe opportunistic infections and cancers

Treatment:

• Currently no cure, but antiretroviral therapy (ART) can control the virus and prevent disease progression
• ART involves taking a combination of HIV medicines (typically three) every day, which prevents HIV from replicating and reduces the viral load in the body

Transmission:

• through direct contact with certain body fluids of a person with HIV, including blood, semen, vaginal fluids, and breast milk

Question 4

Explain essential features of HIV replication with the cell - from entry to exit from the cell

Answer 4

1) Attachment and Entry:

• by attaching its envelope protein, gp120, to the CD4 receptor on the surface of the cell
• This attachment induces a conformational change in gp120, allowing it to bind to a secondary receptor (either CCR5 or CXCR4)
• This triggers another change in the HIV envelope, leading the gp41 protein to facilitate fusion of the viral envelope with the T cell’s membrane
• The viral capsid, which contains two single-stranded RNA genomes and the three vital enzymes (reverse transcriptase, integrase, and protease), enters the host cell

2) Reverse Transcription:

• In the cytoplasm, reverse transcriptase converts the viral single-stranded RNA into double-stranded DNA

3) Integration:

• The newly formed double-stranded viral DNA, along with the integrase enzyme, forms a pre-integration complex which is then transported into the host cell nucleus
• integrase catalyses the integration of the viral DNA into the host cell’s genome

4) Transcription and Translocation:

• Once integrated, the viral DNA, referred to as the provirus, is transcribed and translated using the host cell’s machinery
• Transcription of the proviral DNA creates new viral RNA, which can be used as the genome for new virions, or translated into viral proteins by viral protease

5) Assembly and Maturation:

• the newly synthesised viral proteins and viral genomic RNA assemble at the host cell’s plasma membrane into immature virions
• These virions bud off from the cell, acquiring a piece of the host cell’s plasma membrane as their own envelope
• Following the budding, the protease cleaves the long protein chains into individual functional proteins (like the reverse transcriptase, integrase, and protease enzymes), leading to the maturation of the virus

Question 5

Describe the function of HIV proteins - how new viruses are made from viral proteins

Answer 5

1) Gp120 and gp41:

• These are glycoproteins present on the viral envelope
• Gp120 is responsible for recognising and binding to the CD4 receptor and chemokine co-receptors (CCR5 or CXCR4) on the surface of host cells
• Gp41 facilitates fusion of the viral envelope with the host cell membrane

2) Reverse Transcriptase:

• converting the virus’s single-stranded RNA genome into double-stranded DNA once inside the host cell

3) Integrase:

• integrating the viral DNA (created by reverse transcriptase) into the host cell’s genome
• viral genes to be transcribed and translated using the host’s machinery

4) Protease:

• Protease is responsible for cleaving long chains of HIV proteins into their functional parts
• This occurs after the new virus has budded off from the host cell. The action of protease transforms the immature virion into an infectious particle

5) Gag, Pol, and Env:

• These are the three major genes of HIV
• Gag codes for the matrix, capsid, and nucleocapsid proteins that form the structure of the virus, Gag protein is the precursor
• Pol codes for the crucial enzymes reverse transcriptase, integrase, and protease, pol protein is the precursor protein for Reverse Transcriptase, Protease, and Integrase
• Env codes for gp160, which is cleaved by a host protease into gp120 and gp41, Env protein is the precursor

6) Nef, Tat, Rev, and Vif:

• These are regulatory proteins
• Nef (Negative Factor) enhances viral replication and helps the virus evade the immune system by downregulating CD4 and MHC class I molecules on the host cell surface to evade immune detection
• Tat (Trans-Activator of Transcription) increases the efficiency of viral transcription
• Rev (Regulator of Virion) regulates the export of RNA from the nucleus to the cytoplasm
• Vif (Viral infectivity factor) helps the virus overcome host cell defences by neutralizing APOBEC3G, a protein that would otherwise induce harmful mutations in the viral genome