a nucleic acid surrounded by a protein coat that can only replicate in a living cell

-obligate intracellular parasite

(dependent on host cell)

large viral disease burden- hep B, HIV, etc

1. specific receptors on cell surface

2. endocytosis OR direct fusion of viral envelope with plasma membrane

enveloped viruses

pH dependent entry

induced by drop in pH in endocytic vesicle

influenza A- has an M2 protein with an ion channel that allows virus to acidify and disassemble into the cell- so pH is imp in two parts here.

(the drug amantadine can target this acidification)

enveloped viruses

pH independent entry

direct fusion of viral envelope to plasma membrane

doesn't need pH for conformational change to deposit viral components into cell

non-enveloped viruses

entry

-specific receptors on cell surface

-endocytosis

have developed diff mechanisms, but the point is, they still have to cross the membrane

-have to be more sophisticated than enveloped viruses

tropism

determinants

-host spp (we eliminated smallpox bc it's only found in human)

-receptors:

HIV- CCR5- make them resistant)

influenza A- upper vs lower (ex. avian) resp epithelium

-intracellular env (ex. interferon response-innate immunity, apoptosis, having certain enzymes in cell)

opposite strand of mRNA

aka can't be translated directly into protein

minus strand viruses need their own RNA polymerase (bc humans don't have), then they steal the 5' end of host mRNAs and continue synthesis

Influenza A virus

replication

-minus strand, multisegmented (uncommon)

-*unique: replicates completely in nuc

-viral RNA pol steals 5' end of host mRNA to use as primer, continues synthesis

-uses alternative splicing to make 10 proteins out of 8 segments

Influenza A virus

transcription vs genome replication

TRANSCRIPTION uses RNA pol and the 5' end of host mRNAs (to use as primer)

GENOME REPLICATION doens't do this. it makes a direct copy, transcribed as cDNA (+, an intermediate), which is then copied back to vRNA (-)

translation

how do viruses get multiple proteins

from single segment?

-RNA splicing

-internal translation initiation (IRES- internal ribosome entry site)

-polyprotein

-subgenomic mRNAs

translation initation

how does it work w/o cap?

caps are only in the nucleus, so viruses have developed many diff ways to get around this.

some viruses uses IRES to initiate AUG on its own w/o a cap.

others substitute their own N protein for cap-binding proteins.

a way to get multiple proteins from a single segment.

translates a big protein, then uses its proteases to cleave them into multiple smaller ones.

- RNA pol's very error prone bc they don't have proofing

- multisegments genomes can resassort, leading to genetic variation

1. antigenic drift

from pt mutations, accts for yr to yr shift of flu (ex H1N1 2007 to 2008)

2. antigenic shift

from shuffling of genomes between 2 viruses, accts for complete changes -> outbreaks (ex H3N1 to H1N1)

seen in Influenza A.

from pt mutations, accts for yr to yr shift of flu (ex H1N1 2007 to 2008)

small but significant

-reassortment, from shuffling of genomes between 2 viruses

-complete changes -> outbreaks (ex H3N1 to H1N1)

-little-no pre-existing immunity

-usually occurs in animal reservoir (ex pig)

-potential for pandemic

-innate immunity

viruses stimulate toll-like receptors-> create an interferon response.

target: to prevent translation of virus

-adaptive immunity

body recognizes non-self viral antigens

-> cell-mediated (Tc, Tnk) and humoral (Ab) immunities

pathology of viral infections

direct effects

(direct from virus)

known collectively as Cytopathic Effect (CPE)

-toxicity

-host shut off (ex. turn off translation of host cell mRNAs)

-destruction of cells

-uncontrolled cell division

pathology of viral infections

indirect effects

(as in, immune response to infection)

-destruction of cells

Infection outcomes of viruses

cellular level

-Productive infection (making new infectious particles):

lytic vs nonlytic

-Latency/persistence (stays for a while)

-Abortive infection (virus gets in but can't replicate)

-Oncogenesis

Latency: cells are infected w/ virus, but there's little-no viral expression. ex. herpes

Persistence: virus is surviving in host for long time. ex. chronic infection

All latent viruses are persistent, but not all persistent cells are latent.

Infection outcomes of viruses

organismal level

-local acute disease, ex. rhinovirus-common cold

-systemic disease, ex. adenovirus in txp pts can be fatal

-subclinical replication, ex. persistent viruses. virus happy, host seems to be happy.

-persistence

-chronic infection, ex. hepatitis

-cancer, ex. HPV

-increase severity of secondary infections, ex. dengue- gets more severe the 2nd time you get it

-dose

-site of inoculation (ex. resp virus won't have same effect if it enters through a cut)

-host age and immune status

-other host genetic loci (ex. CCR5 for HIV)

-neutralizing antibodies (bind to virus to prevent infection)

-cell-mediated immunity

-dictated by type of vaccine

Type of Vaccines

Live, attenuated virus

attenuated so that they replicate poorly

-serial passage of virus can lead to loss of virulence

ex. FluMist (influenza A passaged at low temp), MMR, polio, chicken pox

advantage of live vaccine is you get a nice, cell-mediated immune response

-Live, attenuated (cell-mediated response)

(rest are humoral response)

-Killed vaccines- ex. classic influenza, polio

-Subunit- ex. Hep B (one subunit of viral particle)

-Virus-like particles (VLPs)- ex. HPV (viral str's using recomb DNA- taking HP particles grown in E. coli

-Recombinant vaccines

-Passive immunization- administer Ig