Virus-Host cell virus interaction

Chap 1

Define Infectious diseases

**All diseases caused by the transmission of a micro-organism**

**or an infectious agent such as viruses, bacteria, fungi and protozoa.** \n

Define contamination

**Entry of the infectious agent into a host organism**

Define infection

**Pathological consequence at the level of a** __**tissue or an organism**__ **of the** __**abnormal presence**__ **and/or** __**multiplication**__ **of a bacterial, viral or fungal micro-organism**

Define pathogen

**A micro-organism capable of** __**causing disease**__ **in a susceptible host**

Define opportunistic pathogen

**Micro-organism that can become** __**pathogenic in certain situations**__**, particularly when the** __**host’s defenses are disturbed**__

**Contagiousness and mode of transmission depends on ….** \n

Nature of the infectious agent

Severity of infectious varies greatly from …. to….

Benign and self-limiting to severe and complicated life-threatening forms (ex: meningitis)

**Define virulence**

**Quantitative term (infective dose) to indicate the** __**degree of pathogenicity**__ **of a micro-organism and the** __**severity**__ **of the caused disease**

What are the three great plagues ?

HIV

Tuberculosis

Malaria

What is the virus that is considered as an eradicated infectious disease

Polio virus (not circulating) and Smallpox

3 REASONS BEHIND REVERSE SITUATION

1. **Re-emergence of** __**old pathologies**__ **related to changes in human behaviour**
2. **Emergence of** __**new pathogens**__
3. **Emergence of** __**multi-resistant bacteria**__ **with the spectrum of a post-antibiotic era**

What are the leading causes of death worldwide ?

1. Lower respiratory infections
2. Neonatal conditions
3. Diarrhoeal diseases

How can we see a virus ?

under electron microscope , not human eye

What is the size range of a virus ?

20nm

What are the different modes of transmission?

1. Direct contact → HIV, ebola
2. Indirect contact →flu
3. Droplets→flu and ebola
4. Airborne →flu and SARS-Cov
5. Fecal-Oral→HAV,HEV, and rotavirus
6. Pregnancy, delivery and breastfeeding →HIV, HBV, CMV, HSV-1
7. Iatrogenic transmission


1. Medical procedures (syringes…) →HIV,HBV,HCV, CMV
8. Arthropod vector


1. Mosquitos , ticks → Zika, dengue

How zoonotic diseases are transmitted?

1. Airborne
2. Vectors (vector borne diseases from animals)
3. Direct contact with animals
4. Food borne (infected meat and milk)

What are the possible **open doors** for infection?

1. Respiratory airway (Flu)
2. Cutaneous (w/out injury →HSV-1, with a lesion →HIV)
3. Digestive oral (rotavirus)
4. Conjunctival (Adenovirus)
5. Urogenital tract (HSV-2)
6. Inoculation


1. Insect bites (zika and dengue)
2. Bites (Rabies)
3. Intravenous injection (HIV)

How does the virus work first?

__**Surfaces of the body**__ **in relation to the entry and shedding of viruses.**

How can the virus be transmitted in the skin?

1. Arthropods bites → ARBOVIRUS
2. Minor lesions ; multiply in cells of dermis and epidermis → HERPES
3. Major lesions ; bites →RABIES, or soiled materials →HIV

How can the virus be transmitted in the eyes?

Conjonctiva →ADENOVIRUS

How can the virus be transmitted in the respiratory tract ?

1. Aerosol production by coughing and sneezing.

What are the consequences of respiratory infections

1. Local respiratory tract infections (RHINOVIRUS)
2. Generalized infections due to respiratory starting point (MMR)

How can the virus be transmitted through alimentary tract ?

**Fecal-oral transmission through** __**water and food contaminated**__ **with viruses released into the** __**stool.**__

What is the main cause behind the resistance of these viruses in the alimentary tract ?

1. Acidic PH
2. Proteases
3. Bile salts

Give 2 examples of viruses attacking the alimentary tract and their type of consequences.

1. Rotavirus and Enterovirus →Localised infections
2. Poliovirus →Generalised infections

How can the virus be transmitted through urogenital tract ?

Sexually transmitted infections (STI)

Give 2 examples of viruses attacking the urogenital tract and their type of consequences.

1. Localised infections

HSV-2 → Genital herpes

Papillomavirus →Condylomas (genital warts)


2. Generalised infections

HIV or CMV

What are the different routes of excretion of the virus from the body ?

1. Saliva →HSV-1
2. Skin rash → HSV-1 or VZV
3. Respiratory secretions →Flu virus
4. Stool→all GI infections like rotavirus/enterovirus
5. Urine → CMV
6. Blood → HIV
7. Maternal milk →HIV
8. Genital secretions → HSV-2

What are the phases the virus pass through when reaching the __specific entry door?__

Localised/local infection **→** Viremia **→** Generalised/systemic infection

Define localised infection.

**Infection that remains localised to epithelial cells at the primary site of infection.**

**Primary replication of the virus at a site near the entry site.**

Give 2 examples of localised infections

Respiratory infection due to flu virus

Gastroenteritis infection due to rotavirus

What are the factors involved in localisation of the virus

1. **Temperature sensitivity of the virus (diff temp between upper and lower respiratory tract infections)**
2. **Lack of permissiveness of cells**
3. **Polarization of epithelial cells**

Define Viremia

**Passage through the lymphatic system, local lymph nodes and blood dissemination.**

What is the fastest and most efficient route of transmission after primary infection

Blood distribution

Define generalised infection

**Reaching the** __**target organ**__ **where multiplication leads to disease.**

Define viral infection

**Consequence of interaction between** __**viral factors and host response.**__

What defines the duration of infection as __**acute or persistent infections ?**__

**The balance between these viral factors and host response.**

What the the main viral factors ?

* **Mode of release into the organism**
* **Cell tropism**
* **Number of infected cells**
* **Direct or indirect cytopathic effect**
* **Virulence proteins (virus replication)**
* **Escape to the host’s defenses (inaccessible replication sites)**

What are the host’s risk factors ?

1. Extreme ages of life (Newborn and elderly)
2. Pregnancy
3. Hormonal status
4. Innate or acquired immune deficiency (chemo)
5. Malnutrition
6. Chronic diseases
7. Genetic factors
8. Travel to endemic areas
9. Contact with animals

What is the consequence of an imbalance in host factor and virus factor ?

Virus diseases

What are the different types of viral infections?

Starts with acute always then it could be either :


1. Cure and elimination of the virus → Rotavirus
2. Latent infection (primary, latency and reactivation ) - VZV
3. Chronic infection (continued production of the virus ) - HIV
4. Transforming infection (Evolution to CANCER) - HBV or EBV

What is an acute infection ?

When virus replicates and elimination of the virus occurs by the immune response like flu or rotavirus.

Could be symptomatic or asymptomatic

What is a persistent infection

**When the viral genome is maintained in the cell and the virus is not eliminated bu the immune system(replication occurs in the immune cells).**

When it escapes to immune response -→ interact with APC and MHC molecules

Sufficient number of surviving cells with low cytopathic effect

What are the two main categories of persistent infections

1. Latent
2. Chronic

What is a latent infection? Give one 2 examples

* DNA viruses (more stable to persist )
* when it is dormant and possible transmission of the virus during reactivations.
* Examples
* HSAV-1 and 2
* VZV

Where does latency occur ?

**Latency in sites that are characteristic of the virus**

**- quiescent cells: neurons for HSV and VZV** \n **- cells in division: B lymphocytes for EBV**

What is a chronic infection?

Continuous production of viral particles.

Viral transmission for long periods

Viral genome maintained in the host

Which sites does chronic infection persist in?

Organs →Liver such as chronic hepatitis

Heterogenous →Lymph nodes and blood such as HIV

What leads to a persistent infection / chronic

**Inadequate and/or inappropriate immune response**

What are the infectiousness dynamics

What are the 2 main lines of defenses by the body against the virus?

1. Innate immunity (epithelial barriers, phagocytes and NK)
2. Adaptive immunity (B and T lymphocytes , Antibodies and effector T lymphocytes)

What are the consequences of innate immunity against the virus?

Immediate action (several hours)

Orientation of the immune response

Limitation of the damage

Activation of the adaptive response

What are the consequences of adaptive immunity against the virus?

Ability to adapt

Setting up a memory

What happens in primary response

IgM>IgG -→ Early infection

Weak affinity

Low level of somatic hypermutation

What happens in secondary response when several contacts with the virus occurs?

Isotypes of IgG and IgA positive

Strong affinity

High level of somatic hypermutation

Memory antibodies present

What are the different roles of the virus in cell-virus interactions?

Virus →Mandatory parasites

* Depends on the cell for the replication of their genome and production of their components (protein, envelope..)
* Divert the functioning of the cell to their benefit
* Promote the survival of the host cell

What are the different roles of the cell in cell-virus interactions?

* Innate intracellular mechanisms (Apoptosis and autophagy)
* Soluble immune system factors : Interferons (stop translation)
* Adaptive mechanisms

What is cellular machinery

**Viruses have mechanisms for recruiting, adapting, modifying or usurping cellular machinery**

**A large part of the viral genome encodes regulatory molecules**

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How does the virus survive in the host cell?

1. Viral non-structural proteins
2. Virus replication
3. Cell cycle blocking
4. Immortalisation of cells
5. Modulation of cell gene expression
6. Blockage of the splicing of the cell mRNA

What are the different ways used to prevent viral infections?

* **International, national or local health policy**
* **Monitoring and alerting networks**
* **Hygiene**
* **Screening strategies for at-risk patients**
* **Septic isolation of infected or carrier patients**
* **Vaccination policy**
* **Good use policy for anti-infectives: recommendations of scientific societies and consumption monitoring**