Virology

Viruses were widely a mystery until...

the 1930's when the elcetron microscope was invented

Size of viruses

SMALL

*100x smaller than bacteria

*20-150nm in diameter

Characteristics of Viruses

need a living cell

have either DNA or RNA (not both)

have a 'receptor-binding' protein

structure of a virus

nucleic acid

protein coat

lipid envelope

Nucleic Acid

either RNA or DNA

where all herditity information is located(aka viral genome)

must be translated into protein for virus to reproduce

virus needs host cell machinery for transcription/translation of genome

genome may be cirucular, linear, or segmented

Viral genome

the information is the genes for viral proteins

size ranges from 3,000 bp to 200,000 bp

number of genes ranges from 3 to 200 but typically only 10-15 genes

DNA genomes

double stranded

DNA must be transcribed into mRNA, than translated to protein

RNA genomes

single-stranded

have smaller genomes because less stable than DNA

change more rapidly due to no mechanism for repair (up to 2% change a year)

RNA positive stranded

positive sense

acts directly as mRNA

directly translated into protein

no need for transcription

RNA negative stranded

negative sense

contain a "virion-associated" polymerase

transcribes into positive sense mRNA

Protein Coat

Capsid

capsomeres-individual proteins that make up the capsid

2 general shapes- helical, icosahedral

nucleocapsid

nucleic acid with the capsid

Lipid envelope

enveloped viruses have an outer lipid envelope surrounding the protein coat

comes from host cell

have protein spikes sticking out that bind to the host cell

Virion

nucleocapsid + envelope

1 virion= 1 virus particle

Viral classificaiton

genome type (RNA or DNA)

polarity of genome (Pos or Neg)

symmetry of nucleocapsid (helical or Icosahedral)

presence or absence of lipid envelope

Viral infection

infect nearly every life-form on the planet

Virus Life cycle

6-8hrs

1. host cell recognition and binding

2. internalization of genetic material

3. transcription

4. translation of 'early genes'

5. early gene action

6. genome replication

7. translation of 'late' genes

8. assembly

9. release

host cell recognition

viruses have a receptor-binding protein on their surface

binds to receptor on host cell surface (viruses exploit the normal function of the receptor)

Very Specific and Very Strong

Viruses only infect particular types of cells

fusion

virus has fusion proteins on its surface

cause fusion of the viral membrane with host plasma membrane

virla genome enters cytoplasm

internalization

virus gets into the cell

fusion

receptor mediated endocytosis (viropexis)

Receptor-mediated endocytosis

(viropexis)

most common

virus binds to receptor

"coated-pit" forms in cell membrane

inversion of pit around virus allows virus to enter cytoplasm

viral genome enters nucleus/cytoplasm

after internalization....

production of viral proteins

replication of genome

production of viral proteins

1. production of mRNA from DNA (Transcription)

2. production of protein from mRNA (translation)

Production of Viral proteins Positive stranded

genome used directly as mRNA

translated to protein

Polio

Production of viral proteins Neg stranded

RNA genome is complementary to mRNA

Replicase: RNA-dependent RNA polymerase (virus brought into the cell with itself) (makes complementary copy of RNA genome)

Rabies

Retroviruses

RNA virus (HIV)

1. RNA genome transcribed by Reverse Transcriptase (virus-associated)

2. RNA digested and is replaced by DNA (created double stranded DNA)

3. Integrase (virus-associated) integrates DNA into Host cell genome!

4.mRNA is translated to protein

Integrase integrate DNA into host cell genome

viral DNA is now called "pro-viral" DNA

pro-viral DNA is now transcribed to mRNA along with host-cell genome

Reverse Transcriptase

makes DNA copy of RNA (DNA and RNA form double strand)

known as 'RNA dependent DNA polymerase" RNA polymerase II. mRNA is then translated to protein by host-cell. Reverse transcriptase is prone to making many errors that leads to frequent mutation of the virus

DNA Viruses

Viral genome is transcribed to mRNA by host-cell "DNA- dependent RNA polymerase" RNA polymerase II

mRNA is then translated to protein by host-cell

RNA Virus Genome Replication

Replicase (RNA-dependent RNA pol):

*enzyme that synthesizes a complementary RNA strand of RNA genome

*forms double-stand of RNA (unstable)

*New, complementary strand serves as a template for synthesis of new RNA viral genome

Replicase

positive stranded- replicase is translated directly from genome ('early gene')

negative stranded- replicase is carried by virus as a protein

Replication is RAPID

DNA virus genome replication

occurs in nucleus

occurs by formation of "replication fork"

both strands copied simultaneously

RAPID: 100 nuecleotides per second

late genes

genes that are expressed later in the cycle

usually form replicated viral genomes

structural proteins

early genes

genes that are expressed immediately after infection from viral genome

polymerases and enzymes

assembly

viral proteins assemble

capsid forms around nucleic acid

assembly may occur in cytoplasm or at membrane

release- lytic viruses

cell bursts and viruses are released

no envelope

release- enveloped viruses

"bud" from surface

assembly takes place on membrane

virus buds off from membrane

lipid envelope surrounds new virions

Pathogenicity

compares severity of disease caused by Different viruses

Virulence

Compares severity of disease caused by same virus

viruses effects on cellular level

lysis

cells fuse together (syncytia)

malignancy

inclusion bodies

triggers immune response

how disease enters body

invade host

replicate

overcome defenses

spread to other areas via bloodstream

replicate

exit from host

how virus gets in

skin

mucous membranes

transplant

mother to fetus

localized infections

remains at or near site of entry

short incubation period (1-3 days)

generalized infection

spreads to 1 or more organs

not at site of entry

long incubation period (2 weeks)

steps: 1. enter epithelium

2. replicate in epithelium

3. migrate lymph nodes

4. enter bloodstream (fever and fatigue)

5. enters large organs and replicate

6. enter bloodstream and infects target organs

target organs

skin: local or general infection: rash (exanthema)

buccal mucous membrane

lung: local

liver

kidney

CNS

incubation periods

short: 1 week:localized

medium: 1-3 weeks

long: months

extra long: years

patterns of disease

acute non-persistant infection: nearly immediate: single episode

persistent infection with acute onset: primary infection has symptoms: recurring infection b/c of latency (2-3 years after primary infection)

chronic infection: virus continually being produced

R0

reproduction number

average number of secondary cases cause by a single primary case

epidemiology

the study of diseases affect a community

predict trends

guide control measures

evaluate success of control measures

aid in diagnosis

seriological epidemiology

study of the presence of antibodies in the people of a community

antibodies vs age: history of viral infections

charactertistics of the virus

how well doe sit survive between/outside hosts

resist to temp. pH. sunlight/drying

have alternative host?: reservoir or vector

pathogenesis: incubation period

evasivness of immune system: rapid replication at site if infection: mutagenesis

route by which virus shed: skin, feces, blood

characteristics of host

age, sex, ethnic group, occupation, nutrition, immunity

characteristics of environment

geographic location, urban/rural

existence of vectors/reservoirs

socio-economic status (hygiene, overcrowding, education)

prevalence

proportion of a population that are affects by a disease at a given point in time

incidence

the number of cases (per thousand) of a particular disease recorded during a particular PERIOD of time

endemic

refers to a disease that is CONSTANTLY present at a significant level within a community

epidemic

an unusual increase in the number of cases within a community (outbreak)

pandemic

epidemic involving several CONTINENtTS at the same time

herd immunity

proportion of people in a population that are immune to a particular virus

innate immune system components

toll-like receptors; recognize protein spikes/double-stranded RNA

cytokines: interferons (IFNS), chemokines, interleukins

Natural killer cells

interferons

produced/secreted by virus-infected cells

protects neighboring cells freom infection

NOT virus specific

ARE species specific

virus infect through toll receptor; expresses IFNs; IFN diffuse out of cell to neighboring cell receptors; activate enzymes that degrade RNA (stop protein synthesis); activate natural killer cells; enhances ADAPTIVE IMMUNE system

natural killer cells

recognize and kill infected cells

not kill pathogens

"missing-self" cells with low levels of MHC

adaptive immueen system

slow response

has MEMORY

controlled by phagosytic cells and lymphocytes

humoral response or cellular response

Phagocytic cells- dendritic cells or macrophages

lymphocytes- B-cells (plasma/memorycells) T-cells (helper T-cells/cytotoxic T-cells)

Phagocytic cells

macrophages/dendritic cells

phagocytosis

display parts of foreign particles on surface

cells presenting antigen= Antigen-Presenting Cells (APCs)

lymphocytes

specific type of white-blood cell

T-cell in thymus

B-cell in bone marrow

humoral immunity

anti-body mediated

B-lymphocytes; specific type of antibody to specific antigen; stimulatled by helper T-cell reproduces and form plasma B-cells and memory B-cells

Plasma B-cells; IgM (first) and IgG antibodies (longer lasting)

Helper-T cells; bind to APCs displaying antigens; produces Interleukins; stimulate B-cells and cytotoxic T-cells

cell-mediated immunity

cytotoxic T-cells in blood stream kill cells that have foreign antigen

problem because healthy cells might have receptor

vaccines

active immunization- antigen-containing preparation; starts an immune response produce memory B-cells

passive immunization- antibodies from other organism to fight current infection; no memory B-cells

Phage

Phages are specialized viruses that affect bacteria