ways to colonize and breach host surfaces:

-loss of barrier function

-adhesion molecules

-fimbrae, pili

-motility and chemotaxis

-proteases

-surface binding proteins

-bacterial capsules

-toxic proteins

-variability of surface antigens

- evasion and resistance to antibacterial peptides

-iron acquisition compounds

- acquisition of disease

-asymptomatic phase

-prodromal phase

-symptomatic phase

-healing convalescence 

-Nature of disease: tissue target, entry site, accessibility of virus to target tissue; tissue tropism; permissiveness of viral replication ; viral strain

-severity of disease

-cytopathicity

-health status of patient

-virus innoculum

cytopathicity:

3 potential outcomes of a viral infection

1-failed infection--no infection

2-lytic infection--cell death

3-persistent infection--chronic or latent or immortalizing

-herpes viridae family (HHV)

-herpes simplex virus (HSV 1&2)

-varicella zoster virus (VZV)

-epstein barr virus (EBV)

-cytomegalovirus (CMV)

-HHV 6,7,8 (exanthems)

herpes virus characteristics

-ubitquitous, highly infective, small, five sides figure

-ds DNA virus

-DNA envelope has 4basic components

-classified by virulence in cell structure

-viral envelope proteins bind to host cell plasma membrane receptors, enter the cytolasma via endocytosis, virons uncoat, and viral DNA enters host's nucleus

-replication will cause mental swelling

-lack their own metabolism!

-can replicate in both pro/eukaryotic cells

-contain 2 genomes

-coding for structural proteins

-non-coding proteins (enzymes such as RNAase and DNAase, and immune signaling proteins)

attachment

penetration

uncoating of viral nucleic acid

transport of viron

synthesis of mRNA

replication of viral DNA

assembly

dispersion of viron out of cell (egress)

recurrent herpes simplex infections

(7 "phases")

-reactivated virus

-prodromal symptoms

-minimal systemic symptoms

-small group of vesicles (new lesions for 1-2 days)

-viral shedding(3-5 days)

-crusting of vesicles

-healing (9-10 days)

how a virus may get reactivated

-virus hangs out in neural ganglion

-during periods of stress or compromised immune system the virus travels down teh axons like a slinky

-LAT (latency associated transcriptase) keeps virus dormant--when this gene turns off you get prodromal symptoms which are mostly neural (tingly lips, etc.)

-incubation of virus for about 5 days

~day "0" pt experiences systemic and local symptoms

-systemic--> tender lymph nodes

-local->pain/itching/dysuria/malaise/fever/headache

~day 2-5 you see more systemic symptoms

-vesicle, wet ulcer, crusting

-shedding virus for ten days or so!

~day 15 you begin healing

-prodromal symptoms for 1-2 days before day "0"

-day "0" get lesions & local symptoms; shedding virus

~day 10, start to heal

-mostly pallative

-hydration

-antipyretics

-prophylactic tx with acyclovir sometimes

-affects immediate early protein gene transcription and/or early protein phase gene transcription

*thus inhibits DNA elongation/synthesis

-varicella-->chicken pox in kids

-longer incubation period (14-17); prodromal rare

-lesions develop over 3 days

-itchy rash persists for about 1-6 days

-crusting and shedding for about 7 days

-fever 101-105 degreese

-no live attentuated oka vaccine

-zoster-->virus reactivated to cause shingles

-prodrome symptoms common for 4-5 days

-vesicles develop withint 12-24 hrs and rash persists for 1-7 days

-rash forms "belt" or follows CN V1,V2,V3 on face

-pustules dry and crust and fall off

-causes mononucleosis

-tx: supportive

-opportunistic pathogen activated by immunosuppression

-hand-foot-mouth disease

-highly contagious spread by oral fecal route

-herpangia (coxsackie virus)

-vesicles on soft palate

-measles (rubeola)

-vaccine

-german measles (rubella)

-vaccine

-fifth disease (parvovirus B19)

-"slapped cheeks"

-respiratory

-inflammation of the liver

-toxic

-infectious

Types A, B, C, D, E

-infectious

-picornavirus

-capsid RNA

-oral- fecal route

-serum

-hepadnavirus

-enveloped DNA

-sexual contact

-NonA/NonB

-flavivrus

-enveloped RNA

-sexual contact

-Delta agent

-viroid like 

-enveloped circular RNA

-sexual contact

-enteric

-calicovirus \

-capsid RNA

-oral fecal route

-IgM anti HAV or IgM antiHBc indicate recent or active hepatitis infection

-Anti HAV; AntiHbs; Antidelta indicate a past ifnection with hepatitis

-enveloped virion

-very stable and resistant to low pH and temperature extremes

-easy to transmit 

-envelope consists of Hep B surface antigens

-virus binds to hepatocyte

-enters cell endocytotically

-carried to nucleus

-uncoats

-replicates

-goes into membrane vacuole and makes nucleid capsid

-excess capsid particles are released when virus exocytoses

-Acute

-Chronic

-Fulminant

-90% of cases 

-cell mediated immune response shuts down virus and yields resolution

-subclinical, mild, or severe symptoms

-severe classified as having jaundice for 4-5 wks

-incubation period of 4-26 wks

-preicteric phase-prodromal symptoms

-icteric phase-jaundice and dark urine results from build up of bilirubin which liver can't break down

-over period of months

-damage to liver causes spike in liver enzymes

-at beginning you see HBsAg so you know virus is replicating

-towards end you will see anti-HBsAg IgG and yhou know virus is resolved

-between those two stages you have the antigen Hep B window where neither are present in serum bc they are binding each other up.

-9% of cases

-cell mediated immune system doesn't clear virus, but does slow down virus development over span of 6 months +

-half of these cases resolve 

-half of these cases are chronic and active and may cause ultimate damage (cirrhosis and carcinoma)

-in chronic persistant hepatitis, one is asymptomatic, but still sheds the virus

-in chronic active hepatitis, there can be development of carcinoma, cirrhosis, or liver failure but symptoms prior to this point are more mild than acute

-over span of years

-redundancy in liver may cause enzyme levels to fall

-trace the HbsAg & antiHbsAg to detect infectious status

-inactivated HBsAg from human serum (old)

-recombinant DNA vaccine with HBsAg gene inserted into plasmid (current)

-picornavirus

-very stable in environment for long periods of time and can be frozen for months

-liver cell receptors 

-classic RNA replication/cytoplasmic replication

-uncoats and replicates in the cytoplasm

-causes cell to lyse

-usually via oral-fecal route/contaminated food & water

-after ingestion, virus survives low pH of stomach and crosses intestinal wall into blood stream causing transient viremia

-virus gets dumped into liver and the virus causes cell lysis there

-virus is dumped into bile where it still survives and gets dumped back into the intestine

-virus is excreted in fecal matter to start process again

-much shorter incubation period than B

-abrupt onset of symptoms

-children tend to be asymptomatic bc of highly responsive cell mediated immune system]

-virus is small and will stay in circulation even when you see presence of antibodies and virus may deposit elsewhere (cell walls and joints)

-rash and arthritis are rare though

-tx: interupt contamination and give immune serum Ig during incubation phase 

-this is 80-90% effective

-short or long incubation period (avg is about 6-9 wks)

-milder symptoms then Hep A/B

-icteric phase seldome develops

-still see chronic damage though

-10-50% of cases become chronic

-chronic case increases risk of recurrence in liver transplant

-fulminate decreases risk of infectio nof liver transplant

-tx: none; but 10-40% cases respond to interferon and ribivinn tx

-diagnosis: eliminate possibility of other two types

-defective satellite virus

-can't replicate unless Hepatitis B is suprainfected or Co-infected in same cell

-coinfection increases risk of fulminate hepatitis and slightly increases the risk of cirrhosis and carcinoma

-complicates but does not cause hepatitis by itself

-enterically transmitted (oral-fecal route)

-diagnose by excluding other Hep viruses

-similar to HAV clinically

-short incubation time

-abrupt onset of symptoms

-no chronic form

-no tx or prevention

-filterable, small agents

-non living

-require host cell's machinery to replicate

-have either RNA or DNA genome, but not both

-are naked capsid type or enveloped

-must encode any required processes not provided by host cell and package specialized proteins and nuclear binding proteins and enzymes

Naked

DNA/RNA+structural proteins+nuclear binding proteins and enzymes=nucleocapsid

nucleocapsid+envelop (membrane and glycoproteins)=envelope

DNA viruses

name and differentiate between ds or ss, and enveloped or naked

-enveloped: Pox, Herpes, hepadna

-Naked: polyoma, papilloma, adeno and parvo (ss)

-virus has tissue tropism

-attaches to target cell via glycoproteins to bind

-immn syst recognizes these glycoproteins when in circulation after cell lyses

-we use these glycoproteins to create vaccines

-glycoproteins fuse cell membranes to make gigantic cells withe several nuclei

RNA viruses (15)

define if ds or ss; and if + or - stranded

ds: reo

ss+ : picorna, corona, noro, toga, flavi, hepatitis, retro

ss - : orthomyxo, paramyxo, rhabdo, filo, borna, bunya, arena, 

* negative indicates that it is enveloped

-Antibodies prevent virus from attaching

-drugs could stop viral uncoating

-drugs could stop viral transcription and replication

1-recognition and attachment

2-penetration

3-uncoating

4-macromolecule synthesis (mRNA & nonstructural proteins; genome replciation; late mRNA & structural proteins; modification of proteins)

5-assembly

6-budding of enveloped virus OR lysis of non enveloped virus

7-release of virus

viral protein synthesis and protein replication of ds DNA 

-make complement strand of DNA

-make mRNA

-make proteins

-positive stranded RNA is like the mRNA that binds to ribosomes and makes one polyprotein that is then cleaved

-the mRNA makes a template of - RNA to create +mRNA progenies

-RNA is transcribed into mRNA segments and then proteins are made

-RNA is also made into a full length +RNA template to make (-) RNA progenies by RNA polymerase

-acts like (-) stranded RNA 

-transcribed to make mRNA segments by RNA polymerase in capsid

1-necessary

2-DNA synthesis

3-RNA dependent RNA polymerase

-small, nonenveloped icosahedral virus; ds DNA

-encode proteins that promote cell growth

-may oncogenetically transfer a cell that is non permissive

-causes warts and human cervical carcinoma

-infects squamous epithelium & mucosal membrane

-virus accesses the basal cell layer through breaks in skin causing basal cell to grow and cell # increases

-this leads to thickenings and causes the wart/papilloma

-E1 protein binds to DNA @ origin to promote replication

-E6 and E7 are immortalizing genes 

-E6 binds w p53 protein and targets it for degradation

-E7 deactivates p105RB; thus NO BRAKES on cell growth

-like HPV

-T antigen analogous to E6&E7

-JC virus establishes kidney infection

-BK virus establishes latent kidney infection

-respiratory tract-->viremia-->kidney inf.-->viremia-->

-immunocompetent patients experience latency

-reactivation of BK virus causes hemmorrhagic cystitis in urinary tract

-reactivation of JC virus is in the CNS

-capsid made of capsidmeres

-spikes protrude as ligand receptors and are made of glycoproteins

-nonenveloped icosadeltahedron

-potential to become oncogenic

-replication:

-requirements for transcription of early proteins: E1 gene transcription; process of primary transcript; translate immediate early E1A transactivator protein (controll/growth supressor)

-end result is host cell death