BIO313 Exam 4 (REJECTED)

What does hydrophobia mean in the context of rabies?

Hydrophobia refers to the 'fear of water' caused by rabies, affecting the Central Nervous System.

Who developed the first rabies vaccine?

Louis Pasteur and Emile Roux developed the first rabies vaccine using dried spinal cords from rabid animals.

What is the origin of the name 'rabies'?

Comes from the word 'Rabhas', which means 'to do violence'.

What was the state of rabies in 19th Century Europe?

Canine or 'street rabies' was widespread, and the image of a 'mad dog' became a symbol of fear.

How many rabies-related deaths occur annually worldwide?

There are more than 55,000 rabies-related deaths annually.

What are the primary reservoirs of rabies in the U.S.?

Major reservoirs include raccoons, skunks, bats, and foxes.

What characterizes furious rabies in wild animals?

Furious rabies is characterized by excitation, aggressiveness, and biting behavior.

What are the symptoms of dumb rabies in wild animals?

Dumb rabies is characterized by reclusive behavior, drooling, anorexia, and startled responses.

What is the gold standard for diagnosing rabies in animals?

Direct fluorescent antibody (dFA) testing on brain tissue samples.

What does postexposure prophylaxis (PEP) involve?

PEP involves vaccination and immunoglobulin treatment administered after exposure to rabies.

What are the clinical signs of furious rabies in humans?

Signs include hydrophobia, difficulty swallowing, agitation, and hallucinations.

What is the incubation period for rabies?

The incubation period ranges from 5 days to several years, typically around 2-3 months.

What are prodromal symptoms of rabies?

Early nonspecific symptoms include headache, malaise, fever, anorexia, nausea, and vomiting.

What diagnostic methods are used for rabies in humans?

Methods include virus isolation, RT-PCR, serum testing, and skin punch biopsies.

What is the Milwaukee protocol?

A treatment involving coma-inducing medication and antiviral drugs used for rabies survivors.

How does the rabies virus enter the body?

The virus enters via a wound and replicates in muscle cells.

What is the role of acetylcholine receptors in rabies pathogenesis?

The virus uses acetylcholine receptors (nAchR) on peripheral nerves to travel to the spinal cord.

What is the recommended vaccine regimen for rabies pre-exposure prophylaxis?

3 x 1-mL intramuscular shots on days 0, 7, and either 21 or 28.

What is the structure of the rabies virus?

The rabies virus is a bullet-shaped, enveloped -ssRNA virus belonging to the family Rhabdoviridae.

What are Negri bodies?

Negri bodies are viral inclusions within affected cells that confirm rabies infection.

What are fixed strains of rabies virus?

Fixed strains are laboratory strains used for research purposes.

What is the mutation rate of the rabies virus?

The rabies virus has a high mutation rate because the L protein lacks proofreading ability.

What are the symptoms of paralytic rabies in humans?

Symptoms include lack of hydrophobia, weakness leading to ascending paralysis, and lack of hyperactivity.

What is the role of the L protein in rabies virus replication?

The L protein is responsible for RNA-dependent RNA polymerase activity, capping, methylation, and polyadenylation.

What are the secondary symptoms of furious rabies?

Include hydrophobia, agitation, and violent contractions of the diaphragm.

What is the significance of the USDA Wildlife Services in rabies management?

They implement programs for rabies management, including the distribution of oral rabies vaccine baits.

What is the typical duration of rabies disease course after symptom onset?

The disease course lasts 2-14 days before a coma occurs, with death occurring on average 18 days later.

Emerging virus

A virus that has newly appeared in a population or has existed but is rapidly increasing in incidence or geographic range.

Reemerging virus

The reappearance of a known virus after a significant decline in its incidence.

Dengue

An example of an emerging virus; it is an Arbovirus.

Ebola

An example of an emerging virus; it is a Filovirus.

Hantavirus

An example of an emerging virus; specifically Sin Nombre.

Mutation rates

RNA viruses have high mutation rates because their polymerases lack proofreading, allowing them to rapidly adapt to new hosts.

Recombination

The exchange of genetic material between two related viruses infecting the same cell, creating a new hybrid strain.

Reassortment

Occurs in segmented viruses (like influenza) where gene segments are swapped during co-infection, often leading to major antigenic shifts.

Human demographics

Changes in population density and age distribution can create larger pools of susceptible hosts.

Urbanization

Overcrowding and poor sanitation in cities facilitate the rapid spread of viruses like Norovirus or Zika.

Human Movement

Rapid air travel allows a virus to move across the globe in less than 24 hours, often before the traveler shows symptoms.

Norovirus Outbreaks

Highly contagious gastrointestinal virus often spread in closed environments like cruise ships or schools due to its stability and low infectious dose.

West Nile Virus Outbreak

A mosquito-borne virus that emerged in the U.S. (1999) and spread rapidly across the continent, utilizing birds as reservoirs.

Zika Virus

Emerging Flavivirus spread by Aedes mosquitoes; notable for its link to microcephaly and its rapid spread through urban tropical centers.

Zoonoses

Diseases that 'spill over' from animals to humans, often due to increased contact between species.

Viral Hemorrhagic Septicemia (VHS) Virus

An example of a virus affecting agricultural and wild fish populations, highlighting how human environmental impact affects animal health.

Porcine Reproductive and Respiratory Syndrome (PRRS)

A major viral disease in the swine industry often exacerbated by intensive farming.

Dam Construction

Changes in water flow can increase breeding grounds for vectors (like mosquitoes or snails), leading to outbreaks of water-associated diseases.

Food contamination

Globalization means a single contaminated food source can cause multi-state or international outbreaks.

Marburg virus

A hemorrhagic fever virus (similar to Ebola) that can be introduced via the legal or illegal trade of infected primates.

Monkeypox

Emerged in the U.S in 2003 through the exotic pet trade (imported Gambian pouched rats infecting prairie dogs).

Israeli Acute Paralysis Virus (IAPV)

Strongly linked to Colony Collapse Disorder (CCD); can be spread through the global trade of bees and royal jelly.

Cultural Traditions

Practices like the consumption of bushmeat or specific burial traditions (as seen with Ebola) can increase exposure risks.

Nosocomial infections

Diseases acquired within a hospital setting, often affecting the most vulnerable.

Unsafe Injection Practices

Reusing needles can drive outbreaks of bloodborne pathogens like HIV or Hepatitis C.

Contaminated Blood Supply

Historically a route of the spread of emerging viruses before rigorous screening protocols were established.

Immunocompromised Populations

Advances in medicine (organ transplants, chemotherapy) and the HIV pandemic have created a larger population of people with weakened immune systems.

Immunocompromising Viruses

HIV is the primary example, as it destroys T-cells and leaves the host vulnerable to opportunistic infections.

Environmental Disruptions

Natural disasters can displace populations and disrupt sanitation, leading to viral spread.

Climate Change

Warming temperatures expand the geographic range of vectors like mosquitoes and ticks.

Sin Nombre hantavirus outbreak

An outbreak triggered by heavy rainfall (El Niño) which led to a surge in deer mouse population (the reservoir).

History of Cancer and viruses

Approximately 20% of human cancers are associated with viruses.

Rous Sarcoma Virus

In 1911, Peyton Rous demonstrated that a bacteria-free filtrate caused sarcomas in chickens.

src gene

Discovered by Michael J. Bishop and Harold E. Varmus; this gene is found in normal chicken DNA, proving that oncogenes are cellular genes hijacked by viruses.

Cancer causing viruses

At least six viruses contribute to cancer, including HBV, HCV, HPV, EBV, HHV-8 (Kaposi's), and HTLV-1/2.

Oncogene (c-onc)

A gene with the potential to convert a normal cell into a cancerous or transformed cell.

Viral oncogene (v-onc)

A viral gene responsible for the oncogenicity of the virus; often an altered cellular gene.

Proto-oncogene

Normal cellular genes that promote standard cell growth and division.

Tumor suppressor gene

Genes that inhibit the conversion of normal cells to cancer; cancer occurs when these are turned off.

Cell transformation

Changes in morphological, biochemical, or growth properties of a cell.

Cancer

Diseases where abnormal cells divide without control.

Metastasis

When cells separate from a tumor and spread to a new location.

Eukaryotic Cell Cycle

The cell cycle consists of phases (G1, S, G2, M) regulated by checkpoints to ensure proper division.

Changes to regulatory genes

Changes to proto-oncogenes (overactivation) or tumor suppressor genes (inactivation) disrupt checkpoints, leading to uncontrolled growth.

Characteristics of Cancer Cells (in vitro)

Rapid growth, immortalization, loss of contact inhibition (cell pile up), and decreased requirement for serum.

Characteristics of Cancer Cells (in vivo)

Unregulated growth factors, immune evasion, reactivation of telomerases, and increased lytic enzymes.

Cancer Multistep Process

Includes bypassing apoptosis, commanding blood supply (angiogenesis), and escaping immunosurveillance.

Molecular Mechanisms of Retroviruses and Cancer

Involves integration of proviral DNA into host DNA.

Insertional activation of proto-oncogene

Viral promoters or enhancers hyperactivate a nearby cellular proto-oncogene.

Integration of proviral DNA containing v-onc

The virus brings a functional v-onc into the cell, disrupting the cell cycle.

Insertional inactivation of tumor suppressor gene

Integration occurs within a tumor suppressor gene, turning off the cell's natural cancer-preventing mechanism.

Human Endogenous Retroviruses (HERVs)

Make up 8% of the human genome; most are defective but may be cofactors in cancer or autoimmunity.

Human Foamy Virus

Not currently considered pathogenic; potentially a useful vector for gene therapy.

HTLV1/2

HTLV-1 causes Adult T-cell leukemia (ATL) in 2-5% of cases; HTLV-2 is associated with T-cell malignancies.

HIV-1/2

Listed as human retroviruses associated with cancer.

Human Papillomaviruses

Risk categories: low-risk (warts), intermediate-risk (precancerous lesions), and high-risk (cancers like types 16 and 18).

Pap smear

A screening program that has significantly reduced cervical cancer mortality.

HPV structure

Small, nonenveloped, icosahedral, with a circular dsDNA genome.

E6/E7 genes

These integrated genes are overexpressed in cancer, where E6 inactivates p53 and E7 inactivated Rb.

Vaccines

Gardasil 9, Gardasil, and Cervarix.

Oncolytic Viruses

Used to destroy cancer cells without harming healthy ones.

Challenges of Virotherapy

Overcoming host immunity, delivery to the tumor, and using biomarkers to track progress.

Nicotinic acetylcholine receptors (nAchR)

Binds to nicotinic acetylcholine receptors

Low pH-dependent fusion

Fusion with endosomal membranes occurs at low pH

Transport to neuronal cell body

The virus must reach the cell body for replication via the P protein, likely interacting with the dynein-dynactin motor

Uncoating

The acidic interior of the endosome allows the nucleocapsid to escape; M protein dissociates from the RNP

Transcription

L protein transcribed the genome into separate, capped, and polyadenylated +ssRNA transcripts for each gene

Protein synthesis

N, P, M, and L mRNAs are translated by free ribosomes; G mRNAs are translated on the ER and glycosylated in the Golgi

Genome replication

Synthesis of a full-length antigenome begins when sufficient N protein is available

Assembly and release

Occurs once components accumulate; the mature particle buds through the host cell plasma membrane