Viruses and Prions

BI301

viruses infecting eukaryotic cells

-infecting more complex cells

structure of eukaryotic viruses

-same as prokaryotic
-capsid(protein coat)+nucleic acid(DNA or RNA)=nucleocapsid
-naked virus=nucleocapsid only
-enveloped virus=lipid bilayer surrounds capsid

tabacco mosaic virus

-first virus to be discovered
-infects tobacco, tomato, pepper, marigold, others
-naked and ssRNA virus
-serious agricultural pathogen

human papillomavirus

-HPV
-naked and icosahedral virus
-double stranded DNA
-more than 100 types of HPV
-causes plantar and genital warts
-15 types associated with cervical cancer in women and oral cancer males

rhabdovirus

-bullet shape
-envelope virus
-single stranded RNA
-causes rabies
-virus travels via neurons to brain
-eventually infects other parts of body
-negri body: inclusion of replicating rabies virus

ebola

-long, filamentous
-enveloped
-single stranded RNA
-hemorrhagic fever: bleed from orfaces
-reservoir (originates) in bats hunted for food
-kills host too quickly to spread to others easily
-no treatment/vaccine against it
-mortality rate is 60% (chance of dying)

reservoir

natural source for virus or any pathogen
-origin

infection of host cells (eukaryotic)

-similar to phage infection
-steps more complex due to eukaryotic host
-entire virus enters the host cell: nucleocapsid and replication enzymes enter
-replication cycle determines acute (short term) or persistent (long term) infection

stages in virus reproduction in eukaryotic

1. adsorption

2. penetration

3. synthesis

4. maturation

5. release

adsorption in virus reproduction

binding to host cell
-receptor mediated, virus spikes find viral receptors on cell membrane and attach
-viral spikes recognize receptors on cell surface
-dictates host tissue specificity

penetration in virus reproduction

entry into cell, travel to site of replication which is either cytoplasm (RNA virus) or nucleus (DNA virus), just depends on type of virus
-vesicle forms around virus once in cell

synthesis in virus reproduction

-nucleic acid replication, synthesis of viral proteins a
-synthesis of RNA and proteins

maturation in virus reproduction

-assembly of virus
-forms new virus

release in virus reproduction

budding or cell rupture
-infect other cells and/or shed from host
-get out of host cell and diffuse away and can start process over
-leave cell by lysis of host cell to kill it and release virus or can bud off surface
-could cough/sneeze out

tropism

specificity or selective affinity of a virus to host cell, tissue or species
-a pathogen can be restricted to certain areas within a host or only infect specific types of cells.

entry of enveloped virus into host cell: membrane fusion

-penetrations stage
-envelope virus fuses with cell membrane and can be released into cytoplasm
-steps: irreversible attachment-membrane fusion-entry of nucleocapsid-breaks down and RNA is released

entry of enveloped virus into host cell: endocytosis

-natural process
-adsorption triggers endocytosis and virus comes in as it tricks the cell
-steps: specific attachment-engulfment-virus in vesicle-vesicle, envelope and capsid break down-free DNA

viral release: budding

with budding host cell remains intact and slowly overtime produces viruses
-observed in persistent infections
-continual release of virus from cells
-some viruses released via exocytosis from golgi ER

budding of a virus steps

enveloped viruses acquire an external membrane (envelope) by emerging from the host cell membrane, essentially "borrowing" it for their own coat. This process involves the viral core associating with a specific region of the host membrane, which then buds out and pinches off, releasing the virus particle. Budding is a key step in the viral replication cycle, allowing enveloped viruses to exit the host cell and spread.

SARS-CoV-2

severe acute respiratory syndrome coronavirus 2
-3 proteins
1) E protein: envelope protein which is present at site of viral assembly (PER), helps promote budding, protein embedded in viral envelope
2) M protein: role in assembly and viral morphology
3) S protein: spike protein recognizes host receptor, good candidate for vaccine development bc immune system can detect it, gives it the name corona=crown

coronovirus

-many types
-upper respiratory disease
-enveloped
-RNA (ssRNA)
-plus strand RNA (coding: directly translated, starts out with RNA and can be directly coded and translated into DNA)
-large viral genome

replication of coronavirus

-spike proteins recognize ACE2 receptors on respiratory epithelium (adsorption)
-viral genomic RNA (30kb) is translated to produce RNA-dependent RNA polymerase
-viral RNA transcribed fand used as template for viral mRNAs
-viral proteins enter secretory pathway (RER, golgi) complex with nucleocapsid
-viruses exit cell by exocytosisct

cytopathic effects of viral infection

structural changes in host cells caused by viral infection, essentially the visible consequences of viral damage
-fusion of cells and inclusion bodies

fusion of cells

"syncytia" or "giant cell" formation with abnormal function
-cellular syncytia
-cell fusion during viral replication
-neighboring host cells will combine and form syncytia
-Adjacent infected cells can fuse together, forming large, multinucleated cells called syncytia

inclusion bodies

-high concentration of viral particles within a host cell
Viral components or altered host cell structures can accumulate within the nucleus or cytoplasm, forming inclusion bodies.

virions

viral particles

reproductive cycle of retroviruses

-carry reverse transcriptase
RNA->DNA
-viral DNA integrates (by the help of integrase) in host chromosome, is transcribed into viral mRNA then viral mRNA is translated
-translation forms long polyprotein
-viral protease cuts polyprotein into individual viral proteins
-retro=reverse bc it goes backwards in flow of genetic information then forward
-caused by reverse transcriptase enzyme (reads RNA and makes DNA copy from it)

integrase viral enzyme

helps viral DNA integrate into host chromosome

HIV infection

-HIV infects white blood cells, in particular T helper cell of the immune system
-T helper cells: help coordinate many function of the adaptive immune system
-HIV infects then hurts immune system which can lead to diseases like AIDS

structure of HIV

-enveloped virus
-two identical strands of RNA, diploid virus
-viral proteins: protease and, integrase, reverse transcriptase
-spike proteins bind to receptors on white blood cells

steps of HIV virus infection

1) the virus is adsorbed and endocytosed, and the twin RNAs are uncoated. Reverse transcriptase catalyzes the synthesis of a single complementary strand of DNA (ssDNA). the single strand serves as a template for synthesis of a double strand of DNA. in latency, double strand DNA is inserted into the host chromosome as a provirus
2) after a latent period, various immune activators stimulate the infected cell, causing reactivation of the provirus genes and production of viral mRNA
3) HIV mRNA is translated by the cells synthetic machinery into virus components (capsid, reverse transcriptase, spikes) and the viruses are assembled. budding of mature viruses lyses the infected cell. white blood cells decrease

how could you stop HIV virus

have something bind to the spikes of the virus to stop it from docking and fusion
-or target the the protease of HIV viruses with drugs: protease=drug target (ritonavir is inhibitor drug)
-pretty much target the viral enzymes that cause virus replication

categories of viral infection

-acute infection and persistent infection
-based on duration of infection and replication strategy

acute infection

-short duration
-long lasting immunity
-infected cells die, may lyse
-clearance of virus by immune cells, shedding
-virus disappear after disease ends, implies no previous exposure
ex: measles, flu, polio

persistent infection

-viruses always present in body
-new viruses released by budding
-latent, chronic, or slow infections
-long duration, long term infections
ex: chickenpox, hepatitis B, HIV

3 types of persistent infection

-latent, chronic, and slow

latent infection

a state where a pathogen resides in the body without causing noticeable symptoms or active replication. The pathogen can remain dormant for extended periods, even years, and then reactivate, potentially leading to disease

-after initial infection, virus replicates in neurons in non infectious state, virus activated to produce new disease symptoms

chronic infection

a long-lasting infection, often lasting three months or longer, where the pathogen persists and the host's immune system struggles to eliminate it completely

-after initial infection with or without disease symptoms, infectious virus is released from host with no symptoms

-virus is being produced all the time and long period of time and is infectious

slow infection

infections characterized by a long incubation period, often months or years, before clinical symptoms appear. These diseases are typically progressive and often fatal, with the infectious agent remaining in the body for extended periods. Examples include prion diseases like Kuru and Jakob-Creutzfeldt disease
-slow developing disease, transmissible agents multiply without resulting in disease symptoms until they cause a fatal infection

prion diseases

-rare progressive neurodegenerative diseases (progresses over long period of time)
-affects both humans and animals
-brain tissue accumulates spongy lesions
-long incubation period-years between infection and symptoms
-originally thought to be caused by slow virus
-agent identified as a prion
-infectious or spontaneous cases

prion

infectious proteins
-abnormal form of cellular protein that we all have
-goes from normal protein (PrPc) to infectious prion (PrPSc)
-the infectious prion accumulates in brain cells and destroys them and can cause misfolding of the normal proteins and form more infectious proteins
-are transmissible (go from one agent to another)

prion structure

-abnormally folded PrPsc
-aggregate into fibrous structures in the brain referred to as plaque
-disrupt the cell membrane causing cell death
-convert normal prions into abnormal prions

creutzfeldt jakob disease

Chronic, progressive, fatal disease of the central nervous system caused by a prion.
-rare neurodegenerative disease
-3 categories: sporadic, acquired, inherited
-affected brains have spongy appearance
-no treatment or cure

bovine spongiform encephalopathy

Mad cow disease caused by prions.
-transmissible between animal to human by earing the cows