week 4 material Flashcards
what are the characteristics of viruses
- they’re infectious + acellular
- they have to live inside of a host cell and are specific in the host and cell-type they live in
- either have DNA or RNA genome
- has a protein capsid w/ or w/o the phospholipid membrane w/ viral glycoproteins sticking out that surrounds the genome
- they lack genes that code for products that help it reproduce, so it relies on the host cell’s genomes
what is the size range of a virus
20nm - 900nm
what are the different shapes of a virus
helical RNA virus
- capsid in the form of a tube
polyhedral/icosahedral DNA virus
- capsid w/ glycoproteins
enveloped RNA virus
- inner = capsid
- lipid envelope
- viral protein/glycoprotein that is with the lipid envelope
complex DNA virus
- top: head (has DNA inside)
- tail sheath
- tail fiber
*capsomere makes up the protein capsid
how are viruses seen
by a electron microscope
what are bacteriophage
- virus that target and infect bacteria
- it’s structure is that of the complex DNA virus
what is the structure of a virus
contains…
- nucleic acid (DNA or RNA)
- capsid/protein coat (this has the basic necessities/materials to create new virions)
- MAY have envelope (small part of the host cell’s phospholipid bilayer when the virus buds off)
- MAY have spikes (glycoproteins that allows virus to attach to the host cell’s receptors and enter)
what are viral envelopes and the advantages + disadvantages of it
- some virus have envelopes that surround their protein coat
- it is made up of phospholipid bilayer which comes from the host cell’s membrane when the virus replicates or buds off
Advantages
- glycoproteins/spikes on the envelope help to attach to the host cell’s receptors
- considering the the lipid bilayer envelope comes from the host cell, it helps the virus to attack the immune system
Disadvantages
- the envelope makes the virus susceptible to detergents, alcohol, and desiccation
How does virus cause disease
same way as a bacteria
1. maintain a reservoir
2. be transported and enter a host cell
3. adhere, colonize/evade the host cell
4. fight against the host’s defences
5. multiply and complete life cycle
6. chemically or manually damage the host cell
7. leave host cell to go to another or go back to its reservoir
how do viruses attach to host cells
glycoproteins attach/bind to the receptors of the host cell
some viruses fit and some do not
- glycoproteins attach to the adhesion receptors
- virus diffuses
- virus attaches to the entry receptor
what are the steps of the virus life cycle
there are 5 steps
1. attachment
- viruses attach to the host cell via its receptors
- viruses are tissue specific (tissue tropism) - they’re specific in the tissues they’re attacking
2. entry
- either the virus or the genetic material enters the host cell
3. genome replication + gene expression
- the genetic material gets replicated and those genes encode for viral proteins
4. assembly
- new viruses or viral particles get assembled
5. release
- new viral particles leave the cell and infect other cells
what makes up the viruses’ genetic material
- genetic can be either DNA or RNA (single or double stranded)
RNA:
Positive strand
- RNA is translated right away by host cell (it’s like mRNA)
Negative strand
- negative stranded RNA has to be transcribed to positive stranded RNA using RNA dependent RNA polymerase the (virus has to carry its own polymerase)
- then RNA gets translated
DNA:
- positive strand gets transcribed into mRNA
- negative strand is ignored
what are retroviruses + what does provirus mean
these are positive single stranded RNA viruses that create viral DNA
the DNA gets integrated into the host cell’s chromosome
Provirus = what the viral genome that gets integrated is called
what are persistent viral infections + the 2 types
when the virus has not been cleared by the immune system
- latent infections
- chronic infections
what are latent viruses/infections
Latency: when the virus is hidden or inactivated in a host cell
- when this occurs symptoms are not seen and can be difficult to detect
viruses can either…
- have circular viral genome molecules which is outside of the host cell’s chromosome
- have proviruses be integrated in the host cell’s genome
what is an example of a latent virus
chickenpox
- can be contagious
- primary infection: itchy rash that has spread + fluid-filled blisters
- it’s dormant in nerve ganglion (cluster of nerve cells)
- can reactivate later on - travels along the sensory nerves - causes painful + localized skin rash
what are chronic viral infections
when the body is unable to get rid of the viral infection
the virus can impact the immune system using many different mechanisms
- alters the immune cells
- restricts expression of viral genes
- changes viral antigens via mutation
how do we clinically detect viruses
- use electron microscopy
- cytopathic effects: look for cell abnormalities using light microscopy
- enzyme/direct immunoassay: antibodies get used to find and attach to specific antigens
(indirect immunoassay: finding an antibody instead of antigen)
- use nucleic acid amplification tests
how do nucleic acid amplifications work
Genes such as the polymerase, capsid, or envelope gene are conserved among many types/strains of viruses - minimum change to them over time
these genes then become unique or act as signature for that specific virus
this allows for this test to target these genes to help us identify the virus
Can also help with…
- measuring viral load
- monitoring disease progression
- monitoring treatment response
what does host range mean
the types of cells or the range of cells that the virus can infect
each virus has their own range of cells
they can only infect cells that their viral proteins can attach to
what are the different types of host range
wide host range
- e.g. influenza
- infects pigs, birds, humans, etc.
narrow host range
- e.g. HIV
- infects only humans
what are the 2 mechanism that causes for viruses to evolve and invade the immune system
Antigenic drift
- point mutations (1 base) that causes slight change in the spike proteins/glycoproteins
- for influenza - spike proteins HA + NA constantly have antigenic drift - this results in seasonal variations in influenza
- vaccines are updated for each time the spike proteins change
Antigenic shift - big changes in spike protein from reassortment (mixing of genetic material)
- for influenza - 2 different influenza viruses (viruses that come from different species) end up infecting the same host cell + exchange genetic material - this leads to a new strain with the new mix of HA/NA proteins
HIV - what occurs in 1981
there’s reports of high rates of rare pneumonia + cancers in young gay men
before named AIDS - it was GRID (gay-related immune deficiency)
HIV - what occurs in 1982
- cases are NOT only from gay men
- scientists found that AIDS can be sexually transmitted
- started finding cases from patients who got blood transfusion
- cases spread to africa + canada
HIV - what happens in 1983-1984
- cases are reported in 27 countries
- declared an epidemic among straight people in Africa
- US Congress passes the 1st bill to include AIDS research + funding
- WHO holds first meeting to assess AIDS
HIV - what occurs from 1990-2000
1995 - AIDS is the leading cause of death for people ages 25-44
1999 - HIV is the 4th leading cause of deaths worldwide
- new drug combos are created + approved
HIV - what occurs in the 2000’s
2002 - HIV is the leading cause of death in people aged 15-59
US launches PEPFAR - gives 100 billion to combat HIV globally
testing and treatments are continued to be made
public health initiatives are implemented worldwide to decrease transmission
research in women with HIV is starting to get more attention
what is human immunodeficiency virus
- single stranded RNA retrovirus
- passed from human to human via sex, blood, and breast milk
- doesn’t kill host by itself
- targets body’s immune system
HIV = the virus
HIV causes AIDS
AIDS is the disease or condition
what is acquired immunodeficiency syndrome
disease or medical condition that happens when your immune system is too weak to fight infections (due to HIV)
patients die of AIDS-related illnesses - cancer, TB, cardiovascular disease
mostly preventable
what is the taxonomy of human immunodeficiency virus
group = group VI (6) - ssRNA
family = retroviridae
genus = lentivirus
species = HIV-1 + HIV-2 (less common)
what are the features of human immunodeficiency virus
- it’s enveloped
- bullet-shaped capsid
- proteins: reverse transcriptase, protease, integrase
- 2 copies of ssRNA
- 9 genes
how does HIV infect cells
the main target receptors = CD4+
HIV attaches to specific membrane receptors + coreceptors
cells CD4+ receptors are on:
- helper T cells
- macrophages
- dendritic cells
these cells will then also be targeted by HIV
how does HIV reproduce
HIV reproduces by…
- creating complementary DNA inside host cell
- integrate complementary DNA into host cell’s genome
- host cell makes more HIV
what are the steps of HIV’s life cycle
1. binding
- virus (w/ envelope + capsid) binds to the host cells’ receptors and coreceptors
2. fusion
- the viruses’ membrane fuses with the host cell’s membrane
- capsid breaks
- viral RNA + necessary proteins (RT, protease, integrase) are released in the host cell
3. reverse transcriptase
- the RT creates a complementary strand of DNA from the viral RNA
4. integration
- the viral DNA is transported into the nucleus and integrase inserts the DNA into the host cell’s DNA
5. replication
- new viral RNA is made
- HIV uses the host cell’s machinery to build viral proteins (long chains)
- these proteins build new viruses (components of it)
6. assembly
- the new HIV proteins + RNA move to the host cell’s surface
- the viruses form and are not infectious at this time
7. budding
- the HIV pushes out of host cell
- HIV releases protease
- protease breaks up the chains of the viral protein into functioning protein
- HIV is now infectious
how can HIV be transmitted and not be transmitted
By
- sex without protection
- sharing needles
- blood transfusions/contact
- vertical transfer from mom to baby
NOT by
- physical touch
- saliva
sharing cutlery
- showering or swimming pools
- mosquito bites
how does HIV spread
- enters through an opening
- spreads via the bloodstream throughout the body
- reaches the lymph nodes and infects immune cells
how does HIV infect
- HIV binds to the dendritic cells
- HIV enters the dendritic cells as early endosomes
- dendritic cells move to the lymph nodes + HIV gets transferred to CD4 T cells
what is the window period for HIV
this refers to the time where your HIV test results come out as positive after being infected
seroconversion (the production of antibodies in the blood) occurs 3 months after being exposed (for 90% of cases)
- 90% of people will tests positive in the first 3 months of being affected
10% of cases will test positive in the 3-6 months of being affected
what is the disease progression of HIV
Acute infection
Latency phase
- people do NOT show symptoms of being infected with HIV
- seroconversion occurs around the time there’s high spike in the viral RNA
AIDS
- opportunistic infections increase
what does an opportunistic infection mean
an infection caused by a microorganism that normally doesn’t cause a disease but can become pathogenic and cause a disease when the immune system becomes weak
why is HIV hard to treat
- high mutation rate
(~1 mutation occurs for each new genome creates) - extended latency period (long time where an infected person doesn’t show symptoms)
- it integrates its own DNA into the host cell’s genome
what are some antiretroviral therapies
- HIV entry inhibitors
- Nucleoside + Non-nucleoside RT inhibitors
- Integrase inhibitors
- Protease inhibitors
- drugs
Describe the different inhibitors
HIV entry
- targets the entry steps: fusion or coreceptor binding
- prevents the HIV’s envelope from fusing to the host cells
**Nucleoside + Non-nucleoside RT inhibitors
- targets RT
- prevents the synthesis of the complementary DNA
Integrase inhibitors
- targets integrase
- prevents the viral DNA from being integrated into the host cell’s genome
Protease inhibitors
- targets protease
- prevents the long chain of protein from being cleaved into functioning proteins
- mature virions can’t be made
what ended up happening to ARVs + how can we overcome this problem
- led to decline in morbidity (people having AIDS) + mortality
- the viral load would decline and come back up
- this is due to HIV mutating a lot
- some mutations help for HIV to become resistant to the drugs/treatment
Solution
- to use multiple ARVs - they target different points of HIV’s life cycle - called HAART
what are some public health initiatives for HIV
90-90-90 Targets
- for 90% of people have HIV - we want 90% of them to be on treatment - and 90% of those people to have their conditioned to be suppressed or controlled
Treatment as Prevention (TasP)
- prevention strategy designed in BC
- allows for people to have early HIV testing + immediate treatment
- caused for people to have low concentration of HIV in their blood
what does U=U mean
Undetectable = Untransmittable
if people’s viral load is below 40 per mL (undetectable levels) - it can’t be transmitted
what are the disclosure laws
- people do not have disclose they have HIV in every case
- people are expected to disclose they have HIV before sex if there’s a realistic possibility that they are able to transmit it
- there is no realistic possibility that a person can transmit it if their viral load is low/undetectable during the time of sex and a condom was used
what is Pre-Exposure Prophylaxis + Post-Exposure Prophylaxis
PrEP
- people without HIV use this as a preventative measure
- it is a cART - combination of antiretroviral therapy
- decreases their chances of getting HIV
- useful for when one partner has HIV and the other doesn’t or for people who inject drugs
PEP
- it is a cART - combination of antiretroviral therapy
- emergency method for people who have been exposed to HIV
- they take it for a few months after exposure
- they have to start taking it 72 hours after being exposed
