Virology Prof. Dr. Kareem Thamir Al-Kaabi

Objectives of the lecture The main objective of the present lecture is to understand the important chemical substances that make the architecture of any virus. Their arrangement, shape, importance and their role in viral pathogenicity and immunogenicity. At the same time we can understand,more or less, the target of action of different anti viral drugs.

Brief History of virus discovery – Are agents that can’t be seen with an ordinary light microscope – Are agents that pass through filters that can trap even the smallest bacteria – The question that arose was are these agents toxins or poisons? – The Latin word for poison is virus

Basic Virology What is a virus? – Is it living or nonliving? – How are they different from other “living” organisms? Submicroscopic nm in size (10-9 M) Can only be “seen” with an electron microscope Obligate intracellular parasites – Viruses have no genes that encode the proteins that function as the metabolic machinery for energy generation – Viruses have no genes that encode the proteins that function as the metabolic machinery for protein synthesis – Viruses may or may not contain the genes that encode enzymes involved in nucleic acid synthesis

Basic Virology Biochemically – Have RNA or DNA, not both – Have no small ions or polysaccharides (sugars) – May (enveloped viruses) or may not (naked viruses) contain lipids

Some viral shapes adenovirus papillomavirus morbillivirus parvovirus

Basic Virology What is the basic structure of a virus? – Nucleic acid of RNA or DNA – is the genetic information for the virus Single (SS) or double stranded (DS) Linear, circular, or nicked Unsegmented or segmented If SS RNA, may be of the plus (+) or the minus (-) sense + RNA – genomic RNA can serve as mRNA and be directly translated into protein - RNA – genomic RNA cannot serve as mRNA and cannot be translated directly into protein

– Protein outer coat – is called the capsid The capsid is composed of individual subunits called capsomers What is the function of the capsid? – Protects the delicate inner nucleic acid from harsh environmental conditions – May be involved in attachment to host cells There are two basic capsid structures – Icosahedral – Helical

– Viruses that contain only the viral nucleic acid and the capsid are called Non- enveloped (naked) viruses – Some viruses have an outer lipid layer called an envelope The envelope is derived from host cell membranes For viruses that use the plasma membrane as their envelope, the envelope is acquired as the virus exits the host cell via a process called budding Virally encoded proteins in the envelope play a major role in the viral life cycle. – Proteins in the viral envelope are involved in attachment to host cells. – Proteins in the viral envelope mediate fusion of the virus envelope with host cell membrane during the entry of the virus into the host cell.

What is virus? Viruse is a small obligate intracellular parasite, which by definition contain either a RNA or DNA genome surrounded by a protective, virus-coded protein coat. RNADNA

Virus is cell-dependent. For propagation viruses depend on specialized host cells supplying the complex metabolic and biosynthetic machinery

Some viral diseases

VIRUS STRUCTURE Any virus should have a genome which is a type of nucleic acid that could be DNA or RNA not both at all. The nucleic acid could be ss or ds, one piece or segmented,haploid (one copy per a virus) or diploid (two copies per a virus). The genome is surrounded by a protein coat called a capsid, which is made of smaller similar subunits called capsomers. Genome+ capsid= nucleocapsid. some viruses are only nucleocapsids, while others contain an additional outer coat called Envelope which is a lipoprotein membrane, the lipid of it is derived from the host cell membrane and the protein is virus-specific.

What is required for a virus to successfully infect and replicate in a host cell? – In order for a virus to successfully infect a host cell, the cell must contain the receptor that the virus binds to in the process of initiating an infection. The part of the virus that binds to the receptor is called the ligand. The ligand is on the capsid of naked viruses and on the envelope of enveloped viruses. gp 120 (the ligand) on HIV binds to CD4 (receptor) and CXCR4 (co-receptor) on T lymphocytes or CCR5 (co- receptor) on macrophages

Basic Virology – If the cell lacks something required for viral replication, the infection is abortive or non-productive and the host cell is considered to be non-permissive for the virus

What are the basic features of the viral life cycle? – Attachment or adsorption – ligand on virus binds to a receptor on a host cell – Penetration – virus gets inside the host cell Penetration of naked viruses usually involves either: – Receptor mediated endocytosis or – Formation of a pore in the host cell plasma membrane through which the nucleic acid and possibly associated viral proteins enter the cytoplasm

Basic Virology – In order for a virus to successfully replicate in a host cell, the host cell must not only contain the receptor for the virus, it must also have the cellular machinery that the virus needs for replication. – The host range of a virus is the spectrum of host cells that the virus can successfully infect and replicate in. – If the virus successfully replicates in the host cell, the infection is productive and the host cell is said to be permissive for the virus.

Human Immunodefficiency Virus

Basic Virology: – If the cell lacks something required for viral replication, the infection is abortive or non-productive and the host cell is considered to be non- permissive for the virus.

Effects of the virus on the host cell – even though you can’t see the virus, you can see the effects that the virus has on the host cell – Death of the cell – often occurs on release of the virus – Cytopathic effects – are visible effects on the host cell caused by viral replication Inclusion bodies – site of active virus synthesis – Negri bodies of rabies virus Syncytia formation – giant, multinucleated cells formed by the fusion of plasma membranes Chromosomal damage Inhibition of host cell protein, RNA, or DNA synthesis

– Cancer Requires that the virus integrates all or part of its genome into the host cell DNA Only RNA viruses that are retroviruses can cause cancer – they bring in or turn on cellular oncogenes that cause cells to proliferate uncontrollably Many DNA viruses can cause cancer, but they usually do it in a non-permissive cell (cell that lacks something required for viral growth). They usually inactivate tumor-supressor proteins that normally act to keep the cell from going through the cell cycle. Thus the cells start going through the cell cycle and proliferating.