Unit 3 exam review !!!!! (yes)

Virus Features

- Obligatory intracellular parasites (need living cell to multiply)

- Contain DNA or RNA

- Contains protein coat

- Multiply within living host cell (via host cell synthesizing machine)

- no ribosomes

- no ATP-generating mechanism

What is Host Range?

The spectrum of host cells a virus can infect

- most viruses infect only specific types of cells in one host

(Bacteriophages phage receptor either part of bacterial cell wall, fimbriae, or flagella)

(Animal viruses receptor sites are usually on the plasma membrane)

Viral Structure

Virion - complete, fully developed viral particle

- Nucleic Acid: DNA or RNA can be single- or double stranded; linear or circular

- Capsid: Protein coat made of capsomeres (subunits)

- Envelope: Lipid, protein, and carbohydrate coating on some viruses

- Spikes: Projections from outer surface

Nucleic Acid in relation to viruses

- Viral genome is DNA or RNA, never both

- Viral genome may be single-stranded or double-stranded

- Nucleic acid may be linear or circular or segmented

- Total lamount of nucleic acid varies

- From a few thousand nucleotides to as many as 250,000 nucleotides

Capsid and Envelope

Capsid: has a protein coat and is made up of capsomeres (protein subunits)

Envelope: Present in some viruses, external to the capsid

- Composed of lipid, protein, and carbohydrate

- Partially formed from the plasma membrane of the host cell

- Forms when the virus buds from the cell

Spikes: surface carbohydrates and/or proteins

- found on some enveloped viruses

- may be used for attachment

General Morphology

Helical Viruses: Hollow cylindrical capsid that is helical

(ex: viruses that cause rabies/ebola virus)

Polyhedral Viruses (Many-sided): Most are an icosahedron (20 triangular facets and 12 corners)

(ex: adenoviruses and poliovirus)

Enveloped Viruses: most are roughly spherical

Complex Viruses (Complicated Structures)

Example: bacteriophage

Taxonomy of Viruses

Seven groups referred to as "realms"

Genus names end in -virus

Family names end in -viridae

Order names end in -ales

Viral Species: a group of viruses sharing the same genetic information and ecological niche (host)

Baltimore classification system

Distinguished by genome composition and mRNA route

Group I: Double-stranded DNA viruses

Group II: Single-stranded DNA viruses

Group III: Double-stranded RNA viruses

Group IV: (+) sense single-stranded RNA viruses

Group V: (-) sense single-stranded RNA viruses

Group VI: Retroviruses (RNA reverse-transcribing viruses)

Group VII: Pararetroviruses (DNA reverse-transcribing viruses)

Growing bacteriophages in lab

-viruses must be grown in living cells

-bacteriophages are grown in bacteria

- Which are clearings on a lawn of bacteria on the surface of agar

- Each plaque corresponds to a single virus

- Can be expressed as plaque-forming units (PFU)

Growing animal viruses in laboratory

in living animals: mice/rabbits/guinea pigs, some cannot human viruses cannot be grown in animals or can be grown but not cause disease in animal

in embryonated eggs: virus injected into egg, viral growth is signaled by changes or death of embryo, used to grow viruses for some vaccines

In cell cultures - primary cell lines:

-Tissues are treated with enzymes to separate cells

-Cells suspended in a nutrient solution in a tube or special flask—referred to as a primary cell line

-Cells will adhere to container and reproduce to form a monolayer

-Viruses infecting the monolayer are detected via the visible changes or deterioration of the monolayer cells, known as the cytopathic effect (CPE)

-Primary cell lines tend to die out after a few generations; require a continuous source of cells

cell structures for growing animal viruses

cell cultures: may use diploid cell lines derived from human embryos (maintained for about 100 generations)

continuous cell lines: derived from transformed (cancerous) cells

can be maintained indefinitely via HeLa cell line

Viral Identification

Cytopathic effects observed on cell culture

Serological tests: ELISA - virus is detected and identified by its reaction with antibodies

Nucleic acids: PCR

How does a virus multiply?

It must invade a host cell and take over the host's metabolic machinery

A single virion can form tens to thousands of viruses in a host cell

One step growth curve

Lytic Cycle (Multiplication of Bacteriophages)

Phage causes lysis and death of the host cell

ex: tequatrovirus (T-even bacteriophages) that infect E. coli

Lysogenic cycle

phage DNA is incorporated in the host DNA

Phage conversion

Specialized transduction

T-Even (Tequatrovirus) Bacteriophages: Lytic Cycle

Attachment: Phage attaches by the tail fibers to the host cell

Penetration: phage lysozyme opens the cell wall

- Tail sheath contracts to force tail core and DNA into cell

Biosynthesis: production of phage DNA and proteins

- Host cell protein synthesis is halted

Maturation/Assembly:

Assembly of phage particles

Release: Phage lysozyme breaks the cell wall

Lambda Phage Lysogenic Cycle

Not all phages complete the lytic cycle

Temperate Phages (ex. Lambda phage)

- adsorb and penetrate but not induce expression

The viral genome inserts into bacterial genome: becomes an inactive prophage - the cell is not lysed

Prophage is retained and copied during normal cell division - Resulting in the transfer of phage genome to all host cell progeny

Induction can occur resulting in activation of lytic cycle

Induction

Typically triggered by host cell stress

- activates DNA recombinase to cut the prophage out of the genome and initiate the lytic phase

- followed by viral replication and cell lysis

Lysogenic Cycle characteristics

Lysogenic host cells are immune to reinfection by the same phage

Phage conversion: host cell exhibits new properties (encoded by prophage DNA)

Ex: production of diphtheria toxin by Corynebacterium diphtheriae

specialized transduction

- Bacterial genes transferred to another bacterium via a phage

- Changes genetic properties of the recipient bacteria

Multiplication of Animal Viruses

attachment, penetration/genome entry, uncoating, synthesis and assembly, exit and transmission/release

Attachment (adsorption)

Binding of virus to specific molecules on the host cell

Genome entry/Penetration

Viral genome enters the host cell

- Occasionally in an endosome

Uncoating

Viral genome is released from the capsid

Synthesis and Assembly

- Viral components are produced

- New viral particles are constructed

Exit and Transmission/Release

Assembled viruses are released

- By budding (enveloped viruses) or cell lysis (naked viruses)

Biosynthesis of DNA viruses

- Replicate their DNA in the host nucleus, using host enzymes

- Synthesize Capsid proteins in the cytoplasm using host cell enzymes

- Capsid proteins migrate into nucleus where assembly occurs

Adenoviridae

Double-stranded DNA, nonenveloped

Respiratory infections in humans

Tumors in animals

Poxviridae

• Double-stranded DNA, enveloped

• Cause skin lesions (smallpox/MPOX virus)

• Assembly occurs in the cytoplasm

Herpesviridae

Double-stranded DNA, enveloped

HHV-1 and HHV-2—Simplexvirus; cause cold sores

HHV-3—Varicellovirus; causes chickenpox

HHV-4—Lymphocryptovirus; causes mononucleosis

HHV-5—Cytomegalovirus

HHV-6 and HHV-7—Roseolovirus

HHV-8—Rhadinovirus; causes Kaposi's sarcoma

Papovaviricetes

Double-stranded DNA, nonenveloped

Alphapapillomavirus: causes warts, some species can transform cells and cause cancer

Hepadnaviridae

Double-stranded DNA, enveloped

Hepatitis B virus

Use reverse transcriptase to make DNA from RNA

Where do viruses multiply?

in the host cell's cytoplasm via RNA-dependent RNA polymerase

+ strand ssRNA (sense strand)

Viral RNA serves as mRNA for protein synthesis

- Strand ssRNA (antisense strand)

Viral RNA is used as a template for mRNA synthesis

- Requires RNA dependent RNA polymerase provided by virus and packed into virions

dsRNA

- double-stranded RNA

Biosynthesis of RNA viruses

Coronaviridae, Togaviridae, Rhabdoviridae, Picornaviridae, Reoviridae

Coronaviridae

Include SARS-CoV-2 which causes COVID-19 (as well as 4 species that cause mild respiratory infections)

- single-stranded RNA, + strand, enveloped

- Assembly involves the ER and Golgi of the host cell

Togaviridae

- Single-stranded RNA, + strand, enveloped

- alphavirus

- transmitted by arthropods; includes the virus that causes eastern equine encephalitis

Rhabdoviridae

- strand single-stranded RNA

- Lyssavirus - rabies

- Numerous animal diseases

Picornaviridae

+ strand single-stranded RNA, nonenveloped

- Enterovirus - poliovirus and coxsackievirus

- Rhinovirus - common cold

Hepatitis A virus

Reoviridae

Double-strande RNA, nonenveloped

- Reovirus (respiratory enteric orphan)

- Rotavirus (mild respiratory infections and gastroenteritis)

Retroviruses

single stranded RNA, produce DNA

- uses reverse transcriptase to produce DNA from the viral RNA genome

- Viral DNA integrates into host chromosome as a provirus (protected from host's immune system and antiviral drugs)

Retroviridae: Lentivirus (includes HIV), oncoviruses

Viruses and Cancer

Several types of cancers are caused by viruses

- may develop long after a viral infection

- Cancers caused by viruses are not contagious

Sarcoma

cancer of connective tissue

Adenocarcinomas

Cancers of glandular epithelial tissue

oncolytic viruses

infect and kill tumor cells or cause an immune response against tumor cells

(currently being modified and tested as a cancer treatment, some currently in use).

Proto-oncogenes (transformation of normal cells into tumor cells)

genes that encode proteins involved in stimulating normal cell growth

- mutated proto-oncogenes become oncogenes

Oncogenes

genes that transform normal cells into cancerous cells

Transformation

Cells require distinct properties leading to cancer

Oncogenic viruses integrate into the host cell's DNA and induce tumors

DNA oncogenic viruses

• Adenoviridae

• Herpesviridae

Epstein-Barr virus

• Poxviridae

• Papovaviridae

Human papillomavirus

• Hepadnaviridae

Hepatitis B virus

• Retroviridae - HTLV-1/HTLV-2 cause adult T cell leukemia and lymphoma

FelV: feline leukemia virus

Latent virus

- remains in asymptomatic host cell for long periods

- All herpesviruses are capable of latency

- May reactivate due to changes in immunity

- HHV1: cold sores

- Varicellovirus: shingles

persistent viral infection

- occurs gradually over a long period

- is generally fatal

- subacute sclerosing panencephalitis (measles virus)

Plant viruses

- Enter through wounds or via insects

- Plant cells are generally protected from disease by an impermeable cell wall

- Viruses enter via wounds or damage from parasites

- Cause many diseases in economically valuable plants

Plant viroids

short pieces of naked RNA

- cause potato spindle tuber disease

Plant Virusoids

viroids enclosed in a protein coat

- cause disease when plant cell is coinfected with a virus

Prions

Proteinaceous infection particles (PRION = PRotein infectION)

inherited and transmissible through ingestion, tranasplant, wounds

types of prion diseases

Spongiform encephalopathies (neurodegenerative diseases)

- Gerstmann-Straussler-Scheinker syndrome

- Creutzfeldt-Jacob disease (CJD)

- "Mad cow disease"

- Fatal familial insomnia

- sheep scrapie

Types of prions

PrPC: normal cellular prion protein, on cell surface

PrPSc: scrapie protein; accumulates in brain cells, forming plaques

Disease caused by protein misfolding

- conversion of host PrPC into misfolded PrpSC

Pathology

The study of disease

Etiology

The cause of a disease

Pathogenesis

the manner in which a disease develops

Infection

Invasion or colonization of the body by pathogens

Infectious disease

- occurs when an infection results in any change in the state of health

- an infection amy exist in the absence of a detectable disease

- disease may result when a microorganism locates in an area where it is not normally found

Human microbiome

-begins to establish in utero

-more microorganisms acquired from food, people, and pets

-remain throughout life

- estimated to be about 40.000.000.000.000 bacterial cells (10x more than the number of human cells in body)

Human Microbiome Project (HMP)

analyzes relationships between microbial communities on the body and human health

Normal microbiota (normal flora)

permanently colonize the host and do not cause disease under normal conditions

transient microbiota

may be present for days, weeks, or months and then disappear

what is the human microbiome dependent on?

nutrients, physical and chemical factors, mechanical factors, body's defenses against microbes, age/diet/hygiene/lifestyle

plays role in immune system development

vaginal birth

prevalently Lactobacillus and Bacteroides

Cesarean Birth

Microbiome resembles human skin and staphylococcus aureus present

What is Microbial antagonism? (competitive exclusion)

competition between microbes

How does normal microbiota protect the host?

Competing for nutrients

Producing substances harmful to invading microbes

Affecting pH and available oxygen

Clostridium difficle can cause severe intestinal infections if...

normal biota are reduced by antibiotic treatment

replacing normal microbiota can trat C. difficile infections (now done using fecal microbial transfer FMT)

Symbiosis

A close relationship between two species that benefits at least one of the species.

Commensalism

one organism benefits and the other is unaffected

Mutualism

both organisms benefit

Parasitism

One organism benefits at the cost of the other

Robert Koch Experiment

- Obtained Anthrax from affected cow corpse

- Incoulated rabbit with infected blood, killing rabbit

- inoculated second rabbit with blood from first rabbit, killing the second rabbit

- identified long rod-shaped bacilli in blood samples

Koch's Postulates

- The microbe is found in all cases of the disease

- The microbe is isolated from the diseased host and grown in pure culture

- Introducing the microbe into a healthy susceptible host, causes the disease

- The same strain of microbe is obtained from the newly diseased host

Exceptions to Koch's Postulates

1. Some pathogens can cause several disease conditions

2. Some pathogens cause disease only in humans

3. Some microbes have never been cultured

4. Several different pathogens may cause the same signs and symptoms

Symptoms (infectious disease classification)

- subjective changes in body function felt by patient as result of disease

- not apparent to observer

Signs (infectious disease classification)

objective changes in body that can be measured or observed

syndrome

a specific group of signs and symptoms that accompany a disease

communicable disease

a disease spread from one host to another

(ex: covid-19, chicken pox, measles, infleunza, genital herpes, tuberculosis)

contagious disease

a disease that can easily and rapidly spread from one host to another

noncommunicable disease

A disease that is not spread from one host to another

(ex: tetanus)

Incidence

number of people who develop a disease during a paticular time period

Prevalence

number of people who have a disease at a specified time (regardless of when it first appeared), takes into account both old and new cases

sporadic disease

disease that occurs only occasionally

endemic disease

disease constantly present in a population

epidemic disease

disease acquired by many people in a given area in a short time

pandemic disease

worldwide epidemic

Duration

average time that individuals have a disease from diagnosis until either cured or dead

acute disease

symptoms develop rapidly but has a short duration

chronic disease

symptoms develop slowly, likely to last for a long period

subacute disease

intermediate between acute and chronic

latent disease

causative agent is inactive for a time but then activates and produces symptoms

severity

the presence and extensiveness of a disease in the body and its ability to cause death