10. Viruses And Sars Cov Flashcards
– Vero cells
– Vero cells = cells infected with viruses monkey kidney cells that are grown commercially – immortal cells
HeLa cells
– HeLa cells = Henrietta lax, cervical cancer cells, cells are immortal keep growing and don’t die
Viral Structure
- Envelope: Lipid bilayer - membrane acquired as virus buds through the host cell membrane
- Capsid: protein coat for viral genome and proteins
- Can have non envelope viruses only with the capsid and no outer envelope
Proteins on the outside = antigens
Virus genome
- DNA or RNA
- Double stranded
- Single stranded
- Positive or negative sense RNA
- Circular
- Linear
- Most DNA viruses replicate in the nucleus
- Most RNA viruses replicate in the cytoplasm
DNA viruses - 3 examples
Adenoviruses
Hepatitis B virus
Herpes viruses
Adenoviruses
Adenoviruses: ds double stranded DNA, non enveloped
– Respiratory and gastrointestinal infections and conjunctivitis
Hep b
Hepatitis B virus: partially dsDNA, enveloped – circular and slightly double stranded in parts
– Chronic hepatitis, cirrhosis, hepatocellular carcinoma
Herpes viruses: ds DNA enveloped
Herpes viruses: ds DNA enveloped – Herpes simplex (types 1 and 2) – Varicella zoster virus – shingles and chickenpox – Cytomegalovirus – Epstein Barr virus
Hep D
Hepatitis D virus (HDV) is a defective RNA virus which requires the help of hepatitis B virus (HBV) for its replication and assembly of new virions (virus particles). It cannot replicate on its own
RNA viruses
- Influenza virus: ss negative strand RNA , enveloped (RNA dependent RNA polymerase)
- Coronaviruses: ss RNA, enveloped SARS-CoV-2
- Polio: ssRNA, non enveloped
- Hepatitis C: ss positive strand RNA, enveloped
- HIV: ssRNA, enveloped (reverse transcriptase, integrase and viral protease)
Baltimore classification of viruses
—> viruses classifed using this system
• Divide viruses into 7 groups – based on how they use their genetic material to make mRNA
Genetic material —> mRNA —> protein
With RNA you can have two types
• +ve ssRNA
• -ve RNA
• SsRNA has reverse transcriptase to make double strand DNA to make mRNA which makes proteins
Diagnosis of viral infections
- Antigen detection - Hep B detect core antigen, surface antigen, envelope antigen
- PCR – test for SARS-CoV-2 use primers that match a segment of the virus’s genetic material. This allows many copies of that material to be made, which can be used to detect whether or not the virus is present.
- Match segment of genetic material to known virus
- Antibody test – HIV – antibodies to that specific virus
Hepatitis B serology
- Prongs with surface antigen
- Core with geentic material
- Replicate virus in haptocytes
- Release hep E antigen and rise in Hep B surface antigen
- Immune system is exposed in antigen
- Forms anti hep B core antigen antibodies, anti ]bodies to surface and envelop antigens
Viruses and cancer – Human Papillomaviruses
– Some grow in skin, while others grow in mucous membranes such as the mouth, throat, or vagina – spread by contact (touch)
– HPV can cause cervical cancer
– HPV is also implicated in cancers of the penis, anus, vagina, vulva, mouth and throat
Vaccine widely used to prevent HPV infection in young adults
Viruses and cancer – Epstein Barr Virus
- Epstein Barr Virus is responsible for causing infectious mononucleosis (‘kissing disease’)
- Passed from person to person by coughing, sneezing, or by sharing drinking or eating utensils
- Infects and stays B lymphocytes
- Can increase risk of developing nasopharangeal cancer and certain lymphomas, for example, Burkitt lymphoma
Viruses and cancer – HIV
- HIV causes acquired immune deficiency syndrome (AIDS)
- HIV infection increases the risk of cancer, especially some linked to other viruses – Kaposi’s sarcoma - human herpesvirus 8 (HHV8) - human herpes virsu in peopke that are HIV positive cause kaposis sarcoma
Steps in viral replication Viruses undergo similar sequence of events
- Attachment to the appropriate cells
• (eg haemagglutinin of influenza virus or glycoprotein GP 120 of HIV to appropriate cell receptor)- Penetration of virus into cell (endocytosis or fusion of envelope with host cell membrane)
- Uncoating leading to release of their genome and other materials such as enzymes into host cell
- Production of virus specific mRNA resulting in manufacture of virus components
- Assembly of components
Release from target cells and further infection
Death of host cell caused by virus
• Death – the cell is unable to continue functioning normally as the virus takes over for its own multiplication
Transformation of host cell caused by virus
• Transformation – the cell can divide uncontrollably due to activation or introduction of oncogenes
Latent infection of host cell caused by virus
• Latent infection – the virus can remain dormant and does not cause symptoms until it is activated by some factor(s) - eg. Herpes virus becomes latent and cause shingles
chronic infection of host cell caused by virus
• Chronic infection – lasting over a period of time
RNA virus replication
—> RNA viruses normally undergo transcription, translation and replication in the cytoplasm.
Positive sense single stranded RNA
• Positive sense single stranded RNA can function as mRNA and get translated into proteins by the host ribosomes
Negative sense RNA
• Negative sense RNA has to be changed to positive mRNA using the enzyme RNA dependent RNA polymerase to make a positive strand copy which can be read by the ribosomes and result in the manufacture of proteins
DNA virus replication
• Transcription and replication occurs in the nucleus of the infected cells
• Most DNA viruses assemble in the nucleus
– Early transcription (Translation of proteins for DNA replication)
– Late Transcription (Translation of structural proteins)
• Assembly and release
Herpes viruses - antivirals
• Acyclovir, famciclovir and valacyclovir = they act in the same way but are different versions of each other, each is more improved
– stops viral DNA replication by inhibiting DNA polymerase
Flu virus - antiviral
• Tamiflu – inhibits the neuraminidase enzyme on the surface of the virus preventing release of virus
HIV-1 - antivirals
- Triple drug therapy consisting of nucleoside reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor, or a boosted protease inhibitor, or an integrase inhibitor
- Different drugs target different stages of replication – 2 drugs to avoid resistance
HIV virus - serology
- Single stranded positive sense RNA
- Enveloped virus
- Family: Retroviridae
- Genus: Lentivirus
HIV replication
—-> GP120 is a HIV virus antigen binds to CD4 receptor and has to bind to co-receptor
CXCR4 on
• T cells
CCR5 on - cofactor • T cells • Macrophages • Monocytes • Dendritic cells
• Mutation in coreceptor results in resistance to infection
5 Targets for HIV therapy
- Post attachment inhibitors
- Fusion inhibitors
- Reverse transcriptase inhibitors
- Integrase inhibitors
- Protease inhibitors
Retroviral therapy
• Standard antiretroviral therapy (ART) consists of the combination of antiretroviral (ARV) drugs to maximally suppress the HIV virus and stop the progression of HIV disease. ART also prevents onward transmission of HIV.
