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What was rabies known as in the 1880s?
Hydrophobia (fear of water)
Who developed the first rabies vaccine?
Louis Pasteur and Emile Roux
What year was the first human subject injected with the rabies vaccine in?
1886
What is the primary cause of rabies symptoms?
Infection of the central nervous system (CNS)
What are the two forms of human rabies?
Furious (encephalitic) and Paralytic (dumb) rabies
What is the incubation period for rabies?
5 days to several years, usually 2-3 months
What are the primary symptoms during the prodromal period of rabies?
Headache, malaise, fever, anorexia, nausea, vomiting
What is the gold standard for rabies diagnostic testing in animals?
Direct fluorescent antibody (dFA) test
What are the symptoms of furious rabies in wild animals?
Excitation, aggressiveness, biting of objects or other animals
What is the primary rabies reservoir in Asia and Africa?
Dogs
What is the average time from rabies symptom onset to death?
18 days
What is the purpose of postexposure prophylaxis (PEP) for rabies?
To provide passive immunity until active antibodies are produced from the vaccine
What are the three categories of rabies vaccines?
Nerve tissue vaccines, avian embryo vaccines, cell culture vaccines
What is the Milwaukee protocol?
A treatment for rabies survivors involving coma-inducing medication and antiviral drugs
What is the rabies virus's classification?
Family: Rhabdoviridae, Genus: Lyssavirus
What is the structure of the rabies virus?
Bullet-shaped, enveloped -ssRNA virus with glycoprotein spikes
How does the rabies virus enter the host?
Via a wound, replicating in muscle cells and using nicotinic acetylcholine receptors
What is the mutation rate of the rabies virus?
10-4 to 10-5 per nucleotide per cycle of replication
What are the symptoms of paralytic rabies in humans?
Lack of hydrophobia, hyperactivity, seizures, weakness, and ascending paralysis
What is the role of the L protein in the rabies virus?
It functions as RNA-dependent RNA polymerase for transcription and replication
What should you do if bitten by an animal?
Provide information to a physician about the animal, bite circumstances, and vaccination status
What are the secondary symptoms of furious rabies?
Hydrophobia, difficulty swallowing, agitation, anxiety, hallucinations
What is the significance of the rabies vaccine injection schedule?
3 × 1-mL shots on days 0, 7, 21, or 28 to induce immunity
What is the primary symptom of dumb rabies in wild animals?
Reclusive behavior, drooling, anorexia, and loss of fear of humans
What is the incubation period for rabies in humans?
Usually 2-3 months, but can range from 5 days to several years
What is the primary method of rabies transmission?
Through bites from infected animals
What is the role of the glycoprotein (G) spikes on the rabies virus?
They facilitate attachment to host cells
What is the significance of the rabies virus's ability to evade the immune system?
It allows the virus to reach the CNS before symptoms appear
What are the common wildlife reservoirs for rabies in the U.S.?
Bats, raccoons, skunks, and foxes
What receptors does rabies virus bind to for attachment?
Nicotinic acetylcholine receptors (nAchR)
How does rabies virus enter the host cell?
Low pH-dependent fusion with endosomal membranes
What is required for rabies virus transport to the neuronal cell body?
The P protein, likely interacting with the dynein-dynactin motor
What happens during the uncoating phase of the rabies virus replication cycle?
The acidic interior of the endosome allows the nucleocapsid to escape; M protein dissociates from the RNP
What is the role of the L protein in rabies virus replication?
It transcribes the genome into separate, capped, and polyadenylated +ssRNA transcripts for each gene
Where are N, P, M, and L mRNAs translated during rabies virus replication?
By free ribosomes
Where are G mRNAs translated and glycosylated in the rabies virus replication cycle?
On the ER and glycosylated in the Golgi
What initiates the synthesis of a full-length antigenome in rabies virus replication?
Sufficient N protein availability
What occurs during the assembly and release phase of the rabies virus replication cycle?
Mature particles bud through the host cell plasma membrane once components accumulate
What is an emerging virus?
A new or recently identified virus to humans, primarily zoonotic.
What defines a reemerging virus?
A virus that is under control but is making a comeback, increasing in incidence and geographical range.
What is the mutation rate of RNA viruses?
1 mutation per every 10^4 to 10^5 nucleotides.
How many mutations does HIV have for every five genomes?
2 mutations.
What is antigenic drift?
A process seen in influenza viruses where small mutations occur over time.
What is recombination in viruses?
The formation of hybrid viruses resulting from coinfection of cells with two viruses.
What is reassortment in the context of viruses?
Gene swapping or antigenic shift, typically seen in influenza viruses with segmented genomes.
Which human factors drive viral disease emergence?
Demographics such as sex/gender, race/ethnicity, mobility, occupation, and socioeconomic status.
How does urbanization affect viral disease spread?
Higher population densities favor the spread due to crowding, sanitation issues, and healthcare facilities.
What was the impact of air travel on the spread of SARS?
Infected travelers could reach any part of the world in less than 24 hours, facilitating the pandemic.
What was the first major outbreak of Zika virus infections?
Occurred in Yap, Federated States of Micronesia, with 78% of the population infected.
What are zoonoses?
Infectious diseases transmissible from animals to humans or vice versa.
What are the signs of Viral Hemorrhagic Septicemia (VHS) in fish?
Bulging eyes, hemorrhaging, bloated abdomens, and abnormal behavior.
What agricultural practice can expose farmers to zoonotic diseases?
Extending farmland into unused land, especially with rodents carrying viruses.
What is a spillover event in viral transmission?
When a pathogen maintained in a reservoir host successfully infects another animal species.
What is Porcine Reproductive and Respiratory Syndrome (PRRS)?
An economically significant disease in pigs characterized by cyanosis of the ears.
How does dam construction contribute to viral disease outbreaks?
It creates standing water that serves as a breeding ground for mosquitoes.
What is Colony Collapse Disorder (CCD) in bees?
A phenomenon where a significant percentage of beekeeping operations suffer from bee population decline.
What role does cultural tradition play in viral outbreaks?
Certain practices, like washing and kissing the deceased, can spread viruses via blood contact.
What are healthcare-associated infections?
Infections acquired in healthcare settings due to unsafe practices or immunosuppression.
What is the significance of immunocompromised populations in viral infections?
They are at higher risk for infections from viruses like cytomegalovirus and herpes simplex virus.
What is vaccine hesitancy?
Reluctance or refusal to vaccinate despite availability, leading to outbreaks of preventable diseases.
How can environmental changes lead to viral outbreaks?
Disruptions like hurricanes or floods can create conditions favorable for disease spread.
What was the correlation between the 1993 hantavirus outbreak and environmental changes?
Increased rainfall led to more food for deer mice, the virus's carrier.
What is the role of global commerce in viral transmission?
Imported food may contain viral contaminants, especially from developing countries.
What is the significance of the 2005 Marburg hemorrhagic fever outbreak?
It highlighted the risks of zoonotic transmission from hunting and cultural practices.
What is the primary mode of HIV transmission?
Primarily through sexual contact or sharing contaminated needles.
What percentage of human cancers are associated with viruses?
About 20%
Who demonstrated that filterable agents could produce tumors in chickens?
Wilhelm Ellerman and Olaf Bang in 1908
What is the Rous sarcoma virus (RSV)?
A retrovirus that causes sarcomas in chickens, demonstrated by Peyton Rous in 1911.
What did Michael J. Bishop and Harold E. Varmus discover about RSV?
They found that the src gene of RSV is found in the normal DNA of chickens, indicating that oncogenes are cellular genes hijacked by viruses.
Name one virus that contributes to cancer.
Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human papillomavirus (HPV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus, or Human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2).
What is an oncogene?
A gene that has the potential to convert a normal cell into a cancerous or transformed cell.
What is a viral oncogene (v-onc)?
A viral gene responsible for the oncogenicity of the virus.
What are tumor suppressor genes?
Genes that suppress or inhibit the conversion of a normal cell into a cancer cell.
What is metastasis?
When a cell or clump of cells separates from a tumor and spreads to another location.
What are characteristics of cancer cells in vitro?
Genetic changes, immortalization, rapid growth, loss of contact inhibition, anchorage independence, and loss of cell cycle control.
What is angiogenesis in the context of cancer?
The process by which tumors command their own blood supply through new blood vessel formation.
What is the role of retroviruses in cancer?
They can carry oncogenes into a cell, activate cellular proto-oncogenes, and inactivate tumor suppressor genes.
What is the significance of human endogenous retroviruses (HERVs)?
They make up 8% of the human genome and may act as cofactors in cancer, autoimmunity, and schizophrenia.
What is the primary difference between DNA and RNA tumor viruses?
DNA tumor viruses have v-oncs that are essential for viral replication, while RNA tumor viruses do not.
What is Epstein-Barr Virus (EBV) associated with?
Mononucleosis and Burkitt's Lymphoma, particularly in individuals with weakened immune systems.
What genetic aberrations are found in Burkitt's Lymphoma tumors?
Aberrations of chromosomes 8 and either 14, 22, or 2, involving the c-myc gene.
What is the primary risk factor for Kaposi's Sarcoma?
It occurs most often in elderly men of Mediterranean, Middle Eastern, or Eastern European descent and in AIDS patients.
What is the mechanism of oncogenesis for Hepatitis B Virus (HBV)?
HBV can integrate its DNA into the host's genome, leading to liver cancer.
What types of cancers are caused by high-risk Human Papillomaviruses (HPV)?
Cancers of the cervix, vulva, vagina, anus, and penis.
What are the three available HPV vaccines?
Gardasil®9, Gardasil®, and Cervarix®.
What is virotherapy?
The use of oncolytic viruses to target and destroy cancer cells without harming healthy cells.
What are the challenges of virotherapy?
Immunity, delivery, and identifying biomarkers to track progress.
What is the role of the E6/E7 proteins in HPV-related cancers?
They inactivate the products of tumor suppressor genes p53 and pRb.
What is the significance of the Papanicolaou (Pap) smear?
It has reduced cervical cancer mortalities by screening for precancerous lesions.
What is the impact of telomerases in cancer cells?
They contribute to the immortalization of cancer cells by preventing cell death.
What is the role of growth factors in cancer cell proliferation?
Increased or unregulated levels of growth factors lead to uncontrolled cell division.
What is the relationship between carcinogens and c-oncs?
Carcinogens can damage c-oncs, potentially leading to cellular transformation.
How do tumor-associated carbohydrate antigens relate to cancer?
They are changes in membrane structure and function associated with cancer cells.