VIRUS- HOST INTERACTION

 Viruses: obligate intracellular parasite

- Depend on host cells at ALL stages of infectious stages
 Different viruses may affect the same or different host cell metabolism
- Virus-host interactions are DIVERSE and COMPLEX

Types of virus-host interactions

1. Productive infections
- Cytocidal infections
- Productive transformation
- Persistence
2. Non-productive infections
- Apoptosis
- Non-productive transformation
- Latency

Productive Infections

 When viral progeny ate produced from infected cells

 Progeny: from very few to thousands of infectious particles
 Steps in a typical productive viral infection:-
1. Adsorption (attachment)
2. Penetration (uptake)
3. Viral disassembly (uncoating)
4. Synthesis of viral components
5. Assembly of progeny virus particles
6. Release of virions

Cytocidal/Lytic

 When host cells caused to be lysed when progeny virions released

 Cell culture: Cytopathic Effect (CPE)
 CPE: Virus-induced damage to the cell that alters it microscopic appeatance
e.g. Poliovirus – lysis
Smallpox virus – cells rounded up (ballooning)
Adenovirus – clumping of cells
Influena virus – cells rounded up
Etc.
 Host cells – killed!

(I didn’t type out Lytic growth cycle. Because Pak Nasa said: No need lah)

Productive Transformation

 Host cells not killed (lysed) but undergo NEOPLASTIC TRANSFORMATION

 Entire genome integrates into that of host cells
  Expressing ONCOGENES
 Host cells transformed to a state of uncontrolled cell division
 Continuous release of infectious viral progeny usually by budding
 Examples: RNA tumous (oncogenic) viruses
- Human T cell leukemia virus (HTLV-1 and 2)
- Sarcoma viruses (cats, chicken)
- Mammary tumour viruses (mice)
 Persistence
- Infected cells and virus co-exist over a long period of time:
Few weeks to years (or even for a whole lifetime)
- Exact mechanism (??? Not known, yet)
- DI (Defective interfering particles)
Temperature sensitive mutants (ts mutants) and IFN – all implicated
- E.g. Lympocytic choriomeningitis virus in mouse (LCM)

NON PRODUCTIVE INFECTIONS (ABORTIVE)

 The intial stages: same as for productive viral infections

 Then, non-productie infections can have different courses-
- Apoptosis
- Non-productive transformation
- Latency
 May be due to a block on one stage of replication cycle
 Or viral genome may be defective
= Replication cannot be completed
 Viral genome may be too small
e.g. Parvoviridae family needs second “helper” virus such as Adenoviruses
 Or due to mutation

APOPTOSIS

 Early viral replications steps -? Trigger host cell apoptotic response (programmed cell
death)
= Host and virus : no propagation
 Example: Vaccinia virus in Chinese hamster ovary cells
- Cell rounding + condensation of chromatin + fragmentation of DNA
= Blebbing of cell membrane -> break up -> apoptotic bodies

NON-PRODUCTIVE TRANSFORMATION

 Virus infects cell

 Viral oncogene integrate with cell DNA -> transformation of cell
 Transformed cells DO NOT yield infectious progeny virus (= non-productive)
 E.g Papillomavirus (wart viruses) ~ 77 types
Some – causally involved in
 - Canccer of cervix
- Cancer of anogenital region

LATENCY

 Virus 0> primary infection -> Progeny (productive)

Then -> secondary latent infection (usually neural cells – for life)
 Viral genome remains intact during latency in nucleus of host cell
 Can reemerge throughout life (especially when immunity )
 E.g Herpex Simplex (HS)
Herpes Zoster (HSV) – chickenpox and shingles
Epstein-Barr virus (EBV) – infectious mononucleosis, Burkitt’s lymphoma and
nasopharyngeal carcinoma.
 (HSV also known as ‘Kayap’ in Malay)

TRANSFORMATION

 Type of virus-cell interaction

 Properties of cells change dramatically
 Transformed cells have similar properties to tumour cells
 Only members of SOME virus families are able to transform cells
Vis
- Herpesviruses
- Adenoviruses
- Hepadnaviruses
- Papovaviruses
- Poxviruses
 Rare event: 1 in 10^5 cells infected
 Characteristics of transformed cells
- Loss of contact inhibition of growth
- Less requirement for serum factors
- Indefinite number of cell divisions
- Viral antigens expressed
- Fibronectin absent
- Fetal antigens found
- Induction of tumours in experimental animals

Ports of entry – the surfaces:

- Skin
- Mucosa
- Oropharynx and GIT
- Respiratory tract
- Urogenital tract

SKIN
Breached through (injections via):-

 Transcutaenous
 Intervenous

Vectors (usually insects. Arthropod-borne/ARBO)

 Arboviruses
- Togavirus (EEE, WEE, VEE)
- Flavivirus (DG, JE, YF)
- Bunyavirus (Crimean Congo HF)
- Reovirus (Colorado tick fever)
- Rhabdovirus (Kotonkan obodhiang)
 Bite
- Intramuscular
- Rhabdovirus

 Injection (IV drug user, iatrogenic)

- Hep B, C, D
- CMV
- HIV
 STD
- Papilloma
- HSV
- Hep B
- HIV

Skin, mucous membranes, oral and genital fluids, semen & milk

 Few from skin lesions

- HSV (labial transmission
- HV (rare: zoster -> chickenpox)
- Papillomaviruses
- Molluscum contagiosum
- Ebolavirus
 STD: HS type 2 & Papillomaviruses
 Rabies, mumps and EBC – replicate in salivary glands -> discharged into saliva -> oral
cavity
 Semen – Hep B and HIV
 Colostrum & Milk – CMV, Mumps and Rubella
 Blood
- Hep B,C,D
- HIV
- HTLV-1, HTLV-2
- CMB
  Arboviruses – insect
 CMV – urine -> important spread in young children

Mucosa

Oropharynx and GIT

 Enteric viruses
 Togavirus (small & large intestine)
 Hepatitis A
 Poliovirus (replication : lymphoid tissue)
 Echovirus

Lower GIT (anal intercourse)

 Hepatitis B
 Herpes Simplex
 HIV

Respiratory Tract

 Rhinovirus (>100 serotypes. They don’t offer cross protection)

 Myxoviruses
 Adenoviruses
 Herpesviruses
 Poxviruses

Eye

 Herpes simplex
 Herpes Zoster
 Adenovirus