micro sheet # 6 - 5aled Ala-rashaideh

*In this lecture we will talk about certain important features about viruses ,for example:
Stages of virus replication, virus survival , & body response to viral infection .....etc. And
Later when we talk about each group of viruses we will talk in details about these features .

*In general : -virus stability (in the environment ) which depends on the type of virus associated with the presence of coat or capsids or presence of any type of envelope (presence of envelope which means that virus might be susceptible to alcohols (ethanol, methanol....etc.) bcz envelope consists of lipid bilayer (protein) that it susceptible to be destroyed by these disinfectant agents.
- also virus stability in high or low temperature is very important:
$certain viruses can manage to survive in low temperature.
$some of viruses prefer to be stable at wide range of temperature (4-40C)
$most of human viral pathogens (not all ) can not survive in temperature over 60 C.
$Hepatitis & HIV (human viral pathogens ) can survive at boiling temperature.
: according to the last point mentioned ,we as dentists must use full autoclave process ,not just UV lamp for instruments sterilization ,bcz UV may just reduce dose of viruses & does not kill all the viral particles, also dryness is not very effective in killing viruses bcz there is some viruses that can survive in very poor moist environment.
: we must always consider that if we have been very close from infected patient the viruses may shed from his respiratory tract ,or his fluids ,or his skin or his urine or feces sample .........etc, & contaminate our skin, clothes....etc.
*In general: - there is misconception about viruses btw pathologists:
$for example; you may find some viruses inhibit our intestine or oral cavity ....etc,
without causing any disease , & that's what we call it (normal virus body ) exactly like bacteria & they may survive inside our intestine or oral cavity without causing any effect.
& that due to 2 factors :
(1)patient who got these viruses may have some amount of immunity against these viruses ,so he can prevent the process of pathogencity of the virus.
OR
(2)these viruses may be defected ( so it can not produce infection ,due to certain genetic defects or damage to the surface of these viruses so it can not attack surfaces of mucosa of intestine or oral cavity....etc).
$when the viruses managed to our body like mucosa of intestine ,oral cavity , skin …etc, the end result might be clinical features of viral infection .
$ we might be infected but might not recognize process of infection (our body does not observe the infection - asymptomatic infection (subclinician infection) & this ended by what we call it ( latent infection ) like presence of rash ,elevation in temperature ..etc.
$certain type of viruses might infect human cells & might not recognize process of infection ( latent infection ) , but the genome of the virus intergraded in the chromosomes of our infected immune system or our tissue cells especially immunotissues like nervous system , human immuno type cells ...etc, & later after for ex. 10-20 years & once we have certain type of immunodeficiency, the viral genome may be reactivated & result in certain type of disease not necessarily similar to the normal disease resulted from the first infection of the same virus, like chicken pox & developing of shingles.
*Pathogenesis of virus depends on certain factors: 1-according to the type of virus 2- if the virus is enveloped or not 3-site of virus entry 4- if it replicate in certain type of tissues
$& these factors contribute in the relation btw host & virus & control the multiplication of the virus.
$ example ; Influenza virus can not produce any invasion or infection in intestine ,but it related to respiratory mucosa ,so if we inject influenza virus or it enter blood stream by cut in the hand for example ,it will not produce side effects like if it affect respiratory mucosa ,there will be some of fever , & the body get rid of these viruses by producing specific antibodies, but there is some of viruses can enter from respiratory tract & reach blood stream ,& then to CNS & cause form of encephalitis like meningeal encephalitis ,or it can enter blood stream through skin by bites of some insects.
*Process of virus replication ( check the figure in the slides ):
$type of virus associated with the presence of capsid & capsid presents presence of enormous number of capsomeres ,projected from virus attached to the mucosa of respiratory tract ,& on the mucosa there is receptors , & these receptors if allow the surface antigens of the virus ( which is in capsomeres composed of glycoprotein ), & within the cell membrane we have a specific substance called salicylic acid (aminoacetylnerunic acid ) & this specific type of chemical structure allow these receptors to interact ( produce key & lock =bonds) ,& this result at the end that the capsomeres or surface antigens of virus might be in the middle of the cell or might be engulfed .
$in case if it engulfed ( virus &capsomeres ) by the cell membrane & there will be form of vesicles ( include all the parts of virus inside the cytoplasm).
$genome of the virus might be managed to be introduced in cytoplasm of the cell, sometimes we may develop vesicles or endocytosis or might develop invasions by the same mechanism where will be opening in the cell membrane & will produce a form of invasion & allow virus to attach ( receptors first then the genome where it DNA or RNA ).
$according to the composition of nucleic acid of virus ,if it is as positive single stranded RNA or negative or double stranded DNA , here the process of replication begin ,& it begin first to release virus genome & to see if the genome ( according to its composition) already carry the presence of mRNA ,bcz from mRNA, virus can produce ( by metabolic machinery of infected cells ) tRNA ,& later from tRNA, virus can produce the necessary components to produce new viral particles ,& this will be done within the cytoplasm of the human tissues.
$ 1st process of attachment (absorption)
2nd coding in relation to presence of envelope or capsid….etc.
3rd activation within cytoplasm ( preparation of necessary enzymes for developing tRNA & other mechanisms)
-all of this depends on the acceptance of the cells ( bcz sometimes some of the cells might develop destruction to the virus ,especially if there is certain antibodies attached to the surface of cells (memory cells carry specific antibodies attached to the surface of the cells),so the body has already infected to the same virus ,so it produce B cells, cytotoxic B cells & immunoglobulins…etc, & that inhibit process of coding for example or process of attachment……etc.
: if virus managed to the cell, depending on type of virus ,it can produce in few hours, thousands of viral particles ( Range 1000-10000viral particles in each cell).
*These viral particles ,when they accumulated within the infected tissue or cells ,begin to produce two types of mechanisms to be released (Mechanisms of releasing viral products):
1st process of budding from the cell membrane & budding occurs :
-bulging in the cell membrane of infected cells & within this bulging there is a large number of viral verions ( check spelling plz from slides ) (which is infectious & means viral particles ) ,& it will be later separated from the infected cell without destruction of the cell.
:Budding not necessarily to produce damage to the infected cell.
2nd process of cell lysis : viral products produce lysins ( proteins cause damage to the cell membrane to release viral particles & the result is damaging to the infected cell).
: this form of cell lysis depends on the type of the virus , some cause death or cause damage or at least budding to the infected cell.
*Generally ,the release of these viruses are not necessarily to be infectious particles ,that mean just certain percentage of viral particles is infectious which can attack another cells ,like what happened in influenza in upper respiratory tract ,where shed of any tissue in this area may contain million of viruses , & may be some of this shed excreted by goblet cells ,which can affect another person &attack his respiratory tissue cells & so on…..
$some of these viral particles may reach blood stream (lymphatic channels ) ,& once reach blood stream ,& the body response is by production of humoral immunity or specific antibodies.
$excretion may related to tasonon angle (check plz from slides ) (which means viral particles excretes within feces ) , & some of these particles vanished to cross intestinal barrier & it can reach blood stream ( lymphatic channel), & it also can reach CNS ( for example ; Enterovirus type (poliovirus))
: Poliovirus is the causative agent of poliomyelitis.
Route of poliovirus:
Respiratory tract or intestinal tract- blood streammeninges in CNS & cause complications.
$ during the presence of the virus at the start ( the first attach btw viral particles with any part of our body ) , there will be some sort of straggle ,wither the target cells accept this virus or not ( it depends on the immunostates of the host ), for example : if the host has already memory of this virus like body infected to it in past or immunized against it , ( it means host has instruments to resist the attachment of the invasions of the virus , & all that is in relation to immune response),
$it is not necessarily the host has specific cells & means of T or B cells to resist this virus ,it may just change the shape of receptors on the cells which prevent the attachment of the virus.
*generally, immuneresponse can be divided in two parts:
(1) specific (presence of specific antibodies directed against specific type of virus ).
(2)non-specific defenses (physical & physiological host barriers like lysosomes, cytokines in addition to the developing of interferons ).
:Mostly interferons developed in response to viruses ( like infα , infβ & inf γ).
$presence of specific antibodies ,for example in relation to mucosa ,we have IgA, which found in large number on the surface of mucosa and that to prevent the attachment of certain virus especially if they have pervious contact with these viruses .
$ 2nd type which related to humoral antibodies ( which controlled by vesicles of special IgG & IgM antibodies ),& these types of antibodies are against some of viruses which can reach blood stream.
Example : as we know influenza virus multiply in the mucosa of respiratory tract & despite of that ,there will be high production of IgG & IgA antibodies
- IgA control the infection & might later prevent the reinfection by the same virus ( same antigenic structure of certain viruses ) bcz influenza viruses mainly changes its receptors to can attach to the mucosal cell receptors.
- but the presence of IgG which has developed during infection in blood stream ,it might not contribute to resist infection with influenza virus , despite there is a lot of IgG in mucosa surface ,but it has less effect on the influenza virus there.
$Cell-mediated immunity in certain viruses is more important than humoral antibodies, although humoral antibodies might be sufficient to inhibit multiplication of certain viruses.
For example : Measles viruses in children ,humoral & cell-mediated antibodies are important, but in relation to influenza virus or all of viruses related to mucosa viruses , these can not be of that important.
$During viraemic phase of invasion (means when the virus present in blood stream) , here the presence of specific anti bodies like IgG & presence of complement system & opsonizing mechanisms might inhibit multiplication of viruses ,and this depends on the amount of producing what we call opsonizing antibodies & that also depends on the age of the infected person.
$in general ,the age of infected human is very important factor to recognize certain viruses.
Example : infants & children are more susceptible to viruses than adults & elderly ,bcz they ( children ) still do not have enough specific antibodies against viruses in their blood.
-so generally any contact with viruses result in over disease or clinical features, where as in more age , the body can manage to produce specific antibodies (especially humoral antibodies ) & that sufficient to resist a lot of viral infection.
$so age is important factor to understand susceptibility to certain viral infection & to understand host reaction & age of person in relation to each type of viral infection (which will be discussed when we talk about global variance of viruses).
$There are certain viruses like Influenza , Measles that can depress immunoglobulin synthesis which affect process of producing of specific antibodies & process of phagocytosis.
$There are certain viruses like HIV ,Measles , herpes & Mumps , which can multiply directly inside certain immunological cells & resulted in immunodeficiency ( mainly damage to T cells ,decrease in production of T cells ) , ( Especially HIV which not just escape from immunodefenses , but can manage to inside immunity itself & cause immunodeficiency).
: Killing agent in HIV infection is not the virus itself , but it might be bacteria , fungi or parasite , & these produce complications & death to the person.

*Interferons:-
$Definition: cytokines produced in relation to viral infection.
$Interferons considered first line of defense from the host against viral invasion.
$Developing of interferons is related to vesicles of viral infection, but it is not specific to certain type of viral infection ( general against any type of viruses ).
$interferons have 2 important functions :
(1)inhibition the attachment of the virus to the cell membrane of the host (universal function against antigen of the virus ).
(2)increase immunoresponse of the body (Resistance of infected cell against viruses).
$ α interferon : produced by blood mononuclear cells.
$ β interferon : produced by fibroblasts.
$ γ interferon : related to lymph system & produced by T lymphocytes, & to some extent it can be directed to certain type of viruses.
: (α) & (β) interferons is the most important of the humoral antibodies & to resist viral infections.
/_\ In conclusion : presence of interferons contribute to resist viral infections , but it is not specific for a specific viruses , & it is limited to some extent , bcz may be not enough for 100% to resist viral invasion of viruses & developing viral infections & diseases.

*In relation to Physical barriers , there is viruses can not manage to our barriers like mucosa ,& others can , & this depends on type of the viruses & that virus if it can found receptors on the host tissues .
$Example : in relation to skin , we have certain Human Papillomaviruses , which attach till they keratinized the tissue & later if there is any type of injuries or abrasions in the skin the virus will produce embibligation (check plz spelling from slides)of virus in the dermal of skin & develop lesions called ( warts ).
$Other Example : Arboviruses in relation to animals & insects , these viruses can be carried by insects & once these insects bite the skin , they inject the virus which found in their gut into the surface of skin & from the skin virus managed slowly to the blood stream ( lymphatic system ) , & produce systemic disease related to hero fever ( plz check spelling from slides ) ( it means al7moa alsfr2 ) , or other type of CNS infection , producing encephalitis & other severe type of diseases.
: in relation to any type of entry, we must remember that the body resist invasion of the virus ( also bacteria) , by presence of humoral antibodies & cell-mediated antibodies,& according to each type we have always certain type of mechanism of resistance to :
1st prevent access of the virus 2nd inhibit multiplication of virus on every side
$ In relation to Gastrointestinal tract , in addition to the presence of IgA mucosal antibodies ,we have other physiological factors like PH of small & large intestine , for example, certain viruses may not survive at PH of 5or 4 , other can survive at neutral & so on…
-PH of stomach may kill majority of the viruses except Enteroviruses , which can manage to small & large intestine .
-Within the large intestine , PH will be about 8 ( alkaline ), & this might inactivates a lot of viruses , &so it is not easy for certain viruses to manage to the intestine.
-Enteroviruses as an exception can survive at low PH & high PH, where as other Influenza viruses , adenoviruses ,rhinoviruses ….etc. it can reach respiratory tract , where they reach GI tract , they inactivated & killed.
$In relation to genitourinary tract infection, there is few viruses, that can manage to the mucosa of urinary tract due to the same mechanism of PH & so on.
$In relation to the conjunctiva of the eye, not any virus can manage to attach , there is some types which can manage like Enteroviruses , Herpes & Adenoviruses.
$In relation to blood stream, not each type of viruses which managed to the skin or mucosa can manage to blood stream. But some viral antigens may manage to blood stream & reduce process of production of specific antibodies, but that not sufficient to produce viraemic phase & develop systemic infection.
-But some viruses once reach blood stream , in few hours – days can manage to produce large number of viruses like Hepatitis virus (B,C …etc.), where it might multiply in the liver & produce liver cirrhosis…etc.
/_\At the end : entrance of viruses & barriers which found in the body can control process of viral infection.
-developing of over disease (clinical manifestation of viral infection), or may be only associated with asymptomatic or subclinical manifestation of disease.

Microbiology sheet
Done by : Khaled Rashydah
Dr. Asem Shehabi
Date of lect. Sunday 20\2\2011
Week #3 Lect.# 6