Module 7 - Viruses and Pollutants

Obligatory intracellular parasites

They can only replicate within the living cells of their host

Virion

An infectious virus particle

capsid

protein coat

Nucleocapsid

viral genome + capsid

envelope

Some viruses have a lipid membrane around the nucleocapsid

Virus life cycle

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

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

3. Uncoating - viral capsid is degraded – releases the viral genome 

4. Biosynthesis - virus hijacks host cell machinery to replicate, transcribe, and translate viral components 

5. Assembly - new virus particles assemble 

6. Release - virions are released from host cell to continue infecting (budding or lysis mechanisms)

Attachment

Virus interacts with specific cell surface receptors and attaches to the cell

Penetration

viruses enter through phagocytosis (engulfment by the host cell)

Uncoating

the viral capsid is degraded to release the viral genome

Tissue Tropism

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

Biosynthesis

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

Assembly

new virus particles are assembled

Release

virions are release from the host cell to continue infecting (budding or lysis mechanisms)

Mucosa

mucous membrane

Modes of transmission can be ___

direct or indirect

Zoonotic viruses

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

Arboviruses

transmitted by arthropods (mosquitos, ticks) (West Nile, Dengue)

Vectors

living organisms that transmit viruses from one host to another

Mechanical vector

The vector isn’t infected but acts as a vehicle to spread virus

Biological Vector

The vector itself is infected and spread the virus

AIDS

Acquired immunodeficiency syndrome

Syndrome

A condition characterized by a set of associated symptom

Simian immunodeficiency virus (SIVs)

a group of retroviruses that cause persistent, HIV-like infections in at least 45 species of non-human primates

HIV

Human Immunodeficiency virus — types 1 and 2

Pneumocystis jirovecii pneumonia (PJP/PCP)

a severe fungal lung infection, often fatal if untreated, that predominantly affects individuals with severely weakened immune systems, such as those with HIV/AIDS, cancer, or on immunosuppressants

• depletion of CD4+ lymphocytes (WBCs)

Kaposi’s sarcoma

a rare cancer caused by human herpesvirus 8 (HHV-8), creating tumors in blood/lymph vessel linings that appear as red, purple, or brown skin/mouth lesions

• classified as an AIDS-defining illness

opportunistic infections

caused by pathogens that typically don’t cause disease in individuals with a healthy immune system

AIDS is caused by ___

HIV

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)

Antiretroviral Therapy (ART)

a daily medication regimen (pills or injections) that suppresses HIV, preventing it from reproducing and destroying the immune system

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

Nucleoside reverse transcriptase inhibitors — NRTI

a class of antiretroviral drugs used to treat HIV and Hepatitis B by inhibiting the reverse transcriptase enzyme, which prevents viral replication

Non-nucleoside RT Inhibitors (non nukes) — NNRTI

a class of antiretroviral drugs used to treat HIV-1 by binding directly to and inhibiting the reverse transcriptase enzyme

IN strand transfer inhibitor (INSTI)

Block the catalytic domain of IN to prevent binding to dsDNA

IN binding inhibitor (INBI)

Inhibit the conformational change required for strand transfer (insertion into host DNA)

Only ___ are currently approved for clinical practice

INSTIs

Protease Inhibitors

Reversibly or irreversibly bind to the active site to block proteolysis

• Inhibit protease dimerization

Undetectable =

Untransmittable

Stages of HIV Infection

Acute, Chronic, AIDS

Acute HIV

• Develops within 2-4 weeks

• Flu-like symptoms

• HIV rapidly multiplies, destroying CD4

• Highest risk of transmission

Chronic HIV

• HIV replication slows

• Many people asymptomatic

• Untreated infection will lead to AIDS within ~10 years

AIDS stage of HIV

• The body cannot fight infection

• Diagnosed when CD4 count <200 cells/mm3

• Untreated survival rate ~3 years

Acute HIV symptoms

Fever, Chills, Headaches, Night Sweats, Sore Throat, Muscle Aches and pains, joint pain, fatigue, swollen lymph nodes — mainly on neck, mouth ulcers

HIV in fluids primarily associated with presence of ___

live cells

3 Modes of HIV Transmission

Blood, Birth, Sex

Pre-exposure Prophylaxis (PrEP)

• Taken by HIV negative people at high risk of infection (sex & drug use)

• Contains 2 NRTIs (Truvada or Descovy)

• Must be taken every day

• Reduced sexual transmission by >90%

Post-exposure Prophylaxis (PEP)

• Taken by HIV-people who may have been exposed — Sex • Shared needles • Sexually assaulted • Occupational exposure

• Contains a NRTI and a protease inhibitor

• Must be taken within 72 hours of suspected exposure

• Must be taken once daily for 28 days

• Reduced HIV infection by >80%

Pollution

defined as introducing harmful substances (solid, liquid, gas) or any form of energy(light, heat, sound, or radioactivity) into the environment

Pollutants

The harmful elements that damage air, water, and land quality

Bioaccumulation

the gradual buildup of chemicals, such as pesticides or heavy metals, within a living organism's tissues over time, occurring when absorption rates exceed metabolic elimination

Biomagnification

the process by which toxic substances accumulate in living organisms at increasingly higher concentrations as one moves up the food chain.

Microplastics

solid plastic particles composed of polymers, additives, and chemicals

Primary microplastics

manufactured ≤ 5 mm

Secondary microplastics

originate from items > 5 mm because of wear during use, fragmentation in waste management, or fragmentation in the environment

Microplastic elimination depends on ___

particle characteristics and behaviors of individuals

Pyrolysis gas chromatography-mass spectrometry (Py-GC/MS)

used to measure the concentration of MPs in human tissue

Pyrolysis

heating & breaking down components

Gas Chromatography

sorting the pieces

Mass Spectrometry

identifying the pieces by chemical mass

Polarized wave microscopy

uses filtered light to analyze how different materials affect the light or “refract” the light

Birefringent materials

split light into two beams travelling at different speeds, and “polarizers” organize the beams to show bright colours

• crystals, minerals, biological tissue

Bioremediation

the use of microbes to clean up contaminated soil and water

gp120

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

gp41

inserts into the host cell membrane to fuse the cell surface

Protease (PR)

cleaves poly proteins into functional pieces

Reverse transcriptase (RT)

makes a dsDNA copy of ssRNA for integration

Integrase (IN)

integrates DNA viral genome into host genome