Lecture 6.2 - Viruses PDF

Viruses: ◦Need living cells to replicate (obligate intracellular parasites) ◦Use the living cells to synthesise all the constituents of the virus ◦Different viruses grow in different types of cells: ‣ Human ‣ Animals ‣ Bacteria ◦In the laboratory:...

Viruses: ◦Need living cells to replicate (obligate intracellular parasites) ◦Use the living cells to synthesise all the constituents of the virus ◦Different viruses grow in different types of cells: ‣ Human ‣ Animals ‣ Bacteria ◦In the laboratory: ‣ Vero cells ‣ HeLa cells ‣ Baby hamster kidney cells (BHK) Viral structure: ◦Envelope: lipid bilayer - membrane acquired as virus buds through the host cell membrane ◦Capsid - protein coat for viral genome and proteins 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: ◦Adenoviruses: ds DNA, non-enveloped ‣ Respiratory and gastrointestinal infections and conjunctivitis ◦Hepatitis B virus: partially dsDNA, enveloped ‣ Chronic hepatitis, cirrhosis, hepatocellular carcinoma ‣ NOTE - 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 ◦Herpes virus: ds DNA, enveloped ‣ Herpes simplex (types 1 and 2) ‣ Varicella zoster virus ‣ Cytomegalovirus ‣ Epstein Barr virus RNA viruses: ◦Influenza virus: ss negative strand RNA, enveloped (RNA dependent RNA polymerase) ◦Coronaviruses: ss RNA, enveloped ‣ SARS-CoV-2  ◦Polio: ss RNA, non enveloped ◦Hepatitis C: ss positive strand RNA, enveloped ◦HIV: ss RNA, enveloped (reverse transcriptase, integrase and viral protease) Baltimore classification of viruses: Diagnosis of viral infections: ◦Antigen detection - Hep B ◦PCR - test for SARS-CoV-2 use primers that match a segment of the virus' genetic material. This allows many copes of that material to be made, which can be used to detect whether or not the virus is present ◦Antibody test - HIV Hepatitis B serology: Viruses and cancer - Human Papilloma viruses: ◦Some grow in skin, while others grow in mucous membranes such as the mouth, throat or vagina ◦Spread by contact (touch) ◦More than 40 types of HPV can be passed on through sexual contact ◦Most sexually active people are infected with one or more HPV types at some point in their lives ◦At least a dozen of these types are known to cause cancer ◦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 drinks 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) Steps in viral replication: ◦Viruses undergo similar sequences of events: ‣ Attachment to the appropriate cells (e.g. 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 Effect on host cell: ◦When cells are infected with virus, this may result in: ‣ Death - the cell is unable to continue functionally normally as the virus takes over for its own multiplication ‣ Transformation - the cell can divide uncontrollably due to activation or introduction of oncogenes ‣ Latent infection - this virus can remain dormant and does not cause symptoms until it is activated by some factor(s) ‣ 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 can function as mRNA and get translated into proteins by the host ribosomes ‣ 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 Antivirals: ◦Herpes viruses: ‣ Acyclovir, famciclovir and valacyclovir - stops viral DNA replication by inhibiting DNA polymerase ◦Flu virus: ‣ Tamiflu - inhibits the neuraminidase enzyme on the surface of the virus, preventing the release of the virus ◦HIV-1: ‣ 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  HIV virus: ◦Single stranded positive sense RNA ◦Enveloped virus ◦Family - retroviridae ◦Genus - Lentivirus HIV replication: ◦GP120 binds to CD4 receptor and has to bind to a co-receptor ◦CXCR4 on: T cells ◦CCR5 on: T cells, macrophages, monocytes and dendritic cells ◦Mutation in co-receptor results in resistance to infection Targets for HIV therapy: ◦Post attachment inhibitors ◦Fusion inhibitors ◦Reverse transcriptase inhibitors ◦Integrase inhibitors ◦Protease inhibitors Retroviral therapy: ◦Standard antiretroviral therapy (ART) consist 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. ◦Huge reductions have been seen in rates of death and infections when use is made of a potent ARV regime, particularly in early stages of the disease. WHO recommends without any restrictions of CD4 counts