HMB204 - Lecture 7 - Viruses & Pollutants

viruses

-are smallest, simplest, and most abundant microbes on Earth

-they are obligatory intracellular parasites

-lack the basic elements required for growth and replication

obligatory intracellular parasites

-they can only replicate within the living cells of their host

-ex. viruses

what are the 5 basic elements required for growth and replication that viruses lack?

1. nucleotides

2. amino acids

3. lipids

4. carbohydrates

5. machinery needed for protein synthesis (ribosomes. tRNAs)

viral genome (DNA or RNA)

-is surrounded by a protein coat called a capsid

what are the 4 components of a viruses structure?

1. viral genome

2. capsid/nucleocapsid

3. envelope

4. envelope protein

nucleocapsid

-the viral genome + capsid = this

-minimal unit of a virus

envelope

-a lipid membrane around the nucleocapsid

-some viruses have this

capsid

-a protein coat around the viral genome

what does the viral genome contain?

-it contains genetic material that enables replication and transmission (early and late genes)

virion

-an infectious virus particle

what are the 4 types of viruses?

1. helical viruses

2. polyhedral viruses

3. spherical viruses

4. complex viruses

**based on shape

helical viruses

-infects a number of different types of plants

-have a slinky-shaped capsid that twists around and encloses its genetic material

(ex. the Tobacco Mosaic Virus)

what is the structure of a helical virus?

-has an RNA and capsid

polyhedral viruses

-known to cause a range of illnesses from pink eye to pneumonia

-are composed of genetic material surrounded by a many-sided capsid

-usually has 20 triangular faces

(ex. adenoviruses)

what is the structure of a polyhedral virus?

-has DNA, a capsid, and glycoproteins on outer surface

spherical virus

-are essentially helical viruses enclosed in a membrane known as an envelope

-the envelope is spiked with sugary proteins that assist in sticking to and entering host cells

(ex. coronavirus)

what is the structure of a spherical virus?

-has RNA, a capsid, glycoproteins, and an envelope

complex viruses

-infect and kill bacteria

-resemble a lunar lander

-are composed of polyhedral “head” and a helical body (or “tail sheath”) that attach to a cell membrane so that is can transfer its genetic material

(ex. bacteriophage)

what is the structure of a complex virus?

-has a polyhedral head, DNA, tail sheath (helical body), and tail fiber

what are the 6 steps of the virus life cycle?

1. attachment

2. penetration

3. uncoating

4. biosynthesus

5. assembly

6. release

attachment (virus life cycle)

-virus interacts with specific cell surface receptors and attaches to the cell

penetration (virus life cycle)

-viruses enter through phagocytosis (engulfment by the host cell)

uncoating (virus life cycle)

-the viral capsid is degraded to release the viral genome

biosynthesis (virus life cycle)

-the virus hijacks host cell machinery to replicate, transcribe, and translate viral components

assembly (virus life cycle)

-new virus particles are assembled

release (virus life cycle)

-virions are release from the host cell to continue infecting through budding or lysis mechanisms

-in order to keep them propagating down the road

tissue tropism

-the range of tissues/cells in a host that a pathogen (virus, bacteria) can infect

(ex. influenza has this for the respiratory tract)

what is the process of the virus life cycle, specifically in influenza?

1. attachment - influenza virus becomes attached to a target epithelial cell

2. penetration - the cell engulfs the virus by endocytosis

3. uncoating - viral contents are released

4. biosynthesis - viral RNA enters the nucleus, where it is replicated by the viral RNA polymerase

5. assembly - new phage particles are assembled

6. release - new viral particles are made and released into the extracellular fluid. The cell, which is not killed in the process, continues to make new virus

what are the 2 types of mechanisms used to release virions

1. budding

2. lysis

budding

-a mechanism used by enveloped viruses to exit a host cell without destroying it immediately

lysis

-virus produces enzymes, such as holins and lysozyme, that create pores and break down the cell wall, causing the cell to burst

-kills the host to release mature viruses, which then infect new cells

can every virus affect humans?

-no, not every virus can infected humans, some are specific to different organisms

how many viruses are recognized as human pathogens with a diverse range of diseases?

-approximately 30 viruses families are recognized as human pathogens with a diverse range of diseases

when does infection typically occur?

-it typically occurs when viruses come into contact with mucosa or damaged skin

mucosa

-mucous membrane

what are the 6 (various) types of mucosa?

1. nasal mucosa

2. oral mucosa

3. esophageal mucosa

4. bronchial mucosa

5. gastric mucosa

6. intestinal mucosa

what are the 5 diverse ranges of diseases that 30 virus families are recognized as human pathogens for?

1. neurological disorder (HSV)

2. hemorrhagic fever (ebola virus)

3. respiratory disease (influenza)

4. cancer (HPV)

5. immunodeficiency (HIV)

neurological disorder (HSV)

-diseases of the central and peripheral nervous systems including the brain, spinal cord, and nerves that disrupt body function, affecting movement, cognition, and sensation

-is a severe, life-threatening neurological disorder causing brain inflammation, primarily caused by HSV-1

-affects the temporal lobes and causes symptoms like headache, fever, confusion, and hallucinations

hemorrhagic disorder (ebola virus)

-characterized by excessive bleeding
-a severe, often fatal hemorrhagic fever with a 25–90% fatality rate, characterized by sudden fever, intense weakness, and vomiting/diarrhea, often followed by internal/external bleeding

respiratory disease (influenza)

-infections or chronic conditions affecting the airways and lungs, commonly caused by viruses (flu, COVID-19, RSV) or bacteria

-a highly contagious viral infection that attacks the respiratory system, including the nose, throat, and lungs

cancer (HPV)

-a group of diseases characterized by uncontrolled cell growth caused by DNA mutations

-causes almost all cervical cancers and a significant portion of anal, oropharyngeal (throat), vaginal, vulvar, and penile cancers

immunodeficiency (HIV)

-a state where the immune system's ability to fight infection and cancer is compromised, resulting in frequent, severe, or recurrent infections

-a virus that damages the immune system by attacking CD4 T lymphocytes, reducing the body’s ability to fight infections

modes of transmission?

-they can be direct or indirect

what are the various modes of transmission?

1. virus-laden secretions (saliva)

2. excretions (feces)

3. bodily fluids

4. skin lesions

5. droplet inhalation

6. animal bites

7. fomites (contaminated objects →viruses live on these)

8. contaminated food/water

direct transmission

-from physical contact to another person (ex. someone coughing on you, intercourse, handshaking someone who didn’t wash their hands etc.)

indirect transmission

-no direct human-human contact, an intermediate is used (ex. doorknobs, phones, elevator button, food)

what are the 3 types/examples of viruses with animal or arthropod hosts?

1. zoonotic viruses

2. arboviruses

3. vectors

zoonotic viruses

-are those that can be transmitted from animals to humans (Rabies, Bird flu)

arboviruses

-are transmitted by arthropods (mosquitos, ticks) (West Nile, Dengue fever)

vectors

-are living organisms that transmit viruses from one host to another

what 3 organisms are the most common viral carriers?

1. non-human primates (ex. monkey)

2. mosquitoes

3. bats

what are the 2 types of vectors?

1. mechanical vectors

2. biological vectors

mechanical vectors

-the vector isn’t infected but acts as a vehicle to spread virus (ex. flies that land on poop)

biological vectors

-the vector itself is infected and spread the virus

what are vectors influenced by?

-they are influenced by lifespan, eating habits, and how far it can travel

what is the process of mechanical vectors?

1. fly picks up pathogen from fecal matter and carries it on its body

2. fly transfers pathogen to food

3. person eats contaminated food and then gets sick

what is the process of biological vectors?

1. infected mosquito bites uninfected person

2. infection spreads through the persons body and into RBCs

3. second mosquito bites infected person. Mosquito may now transmit infection to another person

human specialist viruses

-primarily or exclusively infect humans

-they have evolved to infect and replicate within human cells

-rely on specific receptors on human cells to facilitate the attachment stage of the viral life cycle

-some are deadly and some go dormant

what are 3 examples of human specialist viruses?

1. HPV

2. measles

3. HIV

syndrome

-a condition characterized by a set of associated symptoms

what does AIDS stand for?

-it stands for Acquired Immuno-Deficiency Syndrome

what is AIDS caused by?

-it is caused by HIV

-and at the time it first started occurring (1981), it was an unknown disease being described in the US

-they didn’t know what was happening at this time

HIV-2

-is mostly found in West Africa

-not as good at spreading

HIV-1

-spread worldwide, driving the HIV epidemic

-not a disease that kills someone within a week, it takes time

what does SIVs stand for?

-it stands for Simian Immunodeficiency Virus

what is the origin story of HIV in SIV

• SIVs infects ~45 nonhuman primate species

• SIV_cpz and SIV_smm crossed species barriers on multiple occasions, generating human immunodeficiency virus (HIV) types 1 and 2

what animal is the natural carrier of SIV

-sooty mangabeys are natural carriers of this

how do chimpanzees acquire SIV?

-they acquired it from other primates (prey)

SIV_cpz

-this is from chimpanzees

SIV_smm

-this is from sooty mangabeys

what was the first name AIDS was given?

-it was first given the name GRID (Gay-Related Immune Deficiency), “gay plague”, “gay syndrome”

what unusual medical reports were found in the USA in 1981?

-report of 5 cases of pneumocystis jirovecii pneumonia (PJP/PCP) among previously healthy young men in LA

→ men showed a depletion of CD4+ lymphocytes (WBCs) needed to fight infection

-soon after, health officials begin reporting a spike in cases of Kaposi’s sarcoma(KS) among gay men in New York (which was usually only found in older individuals with weak immune system)

pneumocystis jirovecii pneumonia (PJP/PCP)

-is an opportunistic infection

-is caused by the atypical fungus pneumocystis jirovecii (from a bronchoalevolar lavage)

-most common cause of life-threatening pulmonary infections in PLWHIV

kaposi’s sarcoma (KS)

-is an opportunistic infection

-cancer cells

-are found in the skin or mucous membranes that line the GI tract

-tumors and lesions appear as purple patches or nodules on the skin and/or mucous membranes

-caused by infection with human herpesvirus 8 AND a weakened immune system (prevents apoptosis)

-as the immune system weakens, the risk of this increases

-classified as an AIDS-defining illness (since its so rare)

PLWHIV

-appropriate way to think about HIV positive

-accounts for 30-40% of PCP cases

-stands for People Living With HIV

-individuals diagnosed with the virus, ranging from early infection to advanced AIDS

do people die from HIV?

-they don't necessarily die from HIV they die from infections they can't not fight due to weak immune system

what is the timeline for when AIDS was found to be caused by HIV?

• 1983 -1984 -Human Immunodeficiency Virus (HIV) was isolated from the blood of an AIDS patient & proven to be the causative agent

• targets the immune system by killing CD4+ white blood cells and eliminating a person's immune response

what happens if HIV is left untreated?

-if left untreated, individuals positive for HIV develop AIDS

-HIV ≠ AIDS, but HIV can lead to AIDS

where is HIV now?

-now, 44.1million people have died from AIDS-related illnesses since the start of the epidemic

why are more new cases of HIV developing in North America?

-due to improper education and funding

-because people have stopped paying close attention to it

RNA retrovirus

-inserts a DNA copy of its RNA genome into the DNA of a host cell, changing the genome of that cell

viral tropism

-targets and kills CD4+ T helper cells (plus macrophages, dendritic cells)

-increasingly weakens the immune system, progressing to AIDS and death by opportunistic infections.

what are 2 antigen presenting cells (APCs)?

1. macrophage

2. dendritic cells

APCs

-take up viruses or virus-infected cells and are activated via PRRs

-migrate to draining lymph nodes and present viral peptides to CD4⁺T cells

CD4⁺T cells

-cell activation, polarization and population expansion

effector T cells

-migrate to infected tissue

what is the HIV-1 virion structure?

envelope (env)

• SU (surface, gp120)

• TM (transmembrane, gp41)

structural (gag)

• MA (matrix, p17)

• CA (capsid, p24)

• NC (nucleocapsid, p7)

enzymes (pol)

• PR (protease, p12)

• RT (reverse transcriptase, p66, p51)

• IN (integrase, p32)

-gRNA → 2 copies of ss gRNA per virion

-membrane

gp120 (surface)

-binds to CD4 receptor and co-receptors (CCR5 or CXCR4)

gp41 (transmembrane)

-inserts into the host cell membrane to fuse to the cell surface

matrix protein (p17)

-coats the inside of viral membrane

capsid (p24)

-forms a cone-shaped coat around ssRNAgenome

nucleocapsid (p7)

-forms a complex with ssRNA

protease (p12)

-cleaves polyproteins into functional pieces

RT (reverse transcriptase)

-makes a dsDNA copy of ssRNAfor integration

integrase (p32)

-DNA viral genome into host genome

membrane (HIV-1 virion structure)

-is formed from infected host cells during budding process

what is the process of HIV replication cycle?

1. binding

2. fusion

3. core delivery

4. reverse transcription initiation

5. import

6. uncoating and reverse transcription completion

7. integration (→ provirus = code for a virus that’s already in our DNA)

8. transcription (→ HIV-1 mRNA)

9. translation

10. assembly

11. budding

12. release and maturation

what happens during the budding mechanism of the HIV replication cycle?

-HIV kills CD4+ cells through this mechanism

antiretroviral therapy (ART)

-the initial regimen includes 3 HIV medications from a minimum of 2 drug classes

-requires daily treatment (must be taken routinely)

-treatment is not curative but increases lifespan and reduces transmission (we only have ways to stop its replication, but not a full-on cure, you have it for life)

-3-drug regiment has reduced AIDS progression by 60-80%

curative

-able to cure disease