Host-virus interaction

Host-virus interaction

Viral and host processes that occur during viral infection which enable both partners to respond to each other

Virulence

Degree of pathogenicity of a micro-organism and the severity of the caused disease

Opportunistic pathogen

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

Latrogenic transmission

During medical procedures

• Syringes, blood-derived drugs, transplants

• HIV, HBV, HCV

Portals of entry for infection

• Respiratory airway

• Alimentary tract

• Conjunctive

• By inoculation (bires, IV injection)

• Cutaneous route (with and without injury)

• Urogenital tract (sexually transmitted)

Release of the virus from the body

• Saliva (EBV, CMV)

• Respiratory secretions (flu)

• Stool (rotavirus)

• Urine (CMV)

• Skin rash (VZV)

• Blood (HIV, HBV)

• Maternal milk (HIV)

• Genital secretions (HIV)

Localized infection

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

Factors restraining localized infections

• Temperature sensitivity of the virus

• Lack of permissiveness of cells

• Polarization of epithelial cells

Viremia

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

Systemic infection

Reaching the target organ where multiplication leads to disease

Risk factors for viral infections

• Extremes ages of life (newborns, elderly)

• Pregnancy

• Hormonal status

• Innate or acquired immune deficiency

• Undernutrition and malnutrition

• Chronic pathologies

• Genetic factors

• Travel to endemic factors

• Contact with animals

Acute infection

• Virus replication

• Elimination of the virus by the immune response

• Symptomatic or asymptomatic

Persistent infection

Maintaining the viral genome in the cell, no elimination by the immune system

• Invisible: no viral antigens, replication in immune cells

• Escape to immune response: interference with APC, expression of MHC

Can be latent or chronic

Latent infection

Primary infection, latency, and reactivation

• Mainly DNA viruses (CMV, HSV, EBV)

• Possible transmission during reactivations

• Latency in characteristic virus sites

Chronic infection

Continuous production of the virus, inadequate immune response (HBV, HCV)

• Long periods

• Persistence sites: organs, lymph nodes, blood

• Innapropiate immune response

Transforming infection

Evolution toward cancer (HBV, EBV)

Host disease and infectiousness dynamics

Antibody respone

1. Primary response: IgM, and slow IgG production, weak affinity

2. Secondary response: IgG, IgA, strong affinity, memory, somatic hypermutation

Cell- virus interactions

Virus is a parasite

• Depend on the cell for the replication of their genome and the production of their components

• Divert the functioning of the cell to their benefit

• Promote the survival of the host cell

Cell and its antiviral defenses

• Innate intracellular mechanisms: RNA interference, apoptosis, autophagy

• Soluble immune system factors: interferons

  → stop translation

• Adaptative mechanisms

Viral use of cellular machinery

Virus has mechanisms for recruiting, adapting, modifying or usurping cellular machinery

Survival of the virus in the host cell

• Virus replication

• Cell cycle blocking

• Immortalization of cells

• Modulation of cell gene expression

• Blockage of splicing of the cell mRNA

Antiviral defense

1. Pattern Recognition Receptors (PRRs) detect viral components

2. Interferons production, immune cell activation or apoptosis

Viral modulation of the antiviral defense

Viruses produce proteins that act as saboteurs: blocking PRR sensing, halting interferon signaling, or overriding the cell's suicide commands

PKR Activation

Protein Kinase R (PKR) activation via stress or cytokines inducing:

1. Phosphorylation of eIF2α → translation inhibition

2. Activation of ADD/Caspase-8 pathway → apoptosis

3. Release of NF-kB → antiviral genes activation

Inhibition of PKR by many virus

• Hiding of dsRNA via proteins (NS1 or σ3) → no PKR activation

• US11 blockage

• Mimic of eIF2α via K3L → no eIF2α phosphorilation