Viruses are present as parasites in all organisms. Viruses don't metabolize (no respiration, no ATP synthesis) and they can not replicate on their own. Viruses consist basically of
DNA (or RNA) which is embedded in a protein coat (capsid). Some viruses have an envelope which surrounds the capsid. The envelope consists of a lipid membrane that is studded with proteins (spikes). Viruses are very small, between 17 nm and 1000 nm in diameter. Viruses have different morphologies such as a helical and a polyhedral shaped capsid with or without envelope. In addition to these forms, bacterial viruses can have very complex shapes such as T4 phage. The following figure show the various virus morpholgies (taken from " Mircobiology, G. Tortora, B. Funke, C. Case, Benjamin
Cummings Publ. Co.")

Bacteriophages (phage is the name for a bacterial virus) reproduce by a lytic or a lysogenic cycle. Fig. 13.2
Lytic Cycle : We have seen earlier in the Hershey and Chase experiment that bacteriophage T4 injects its DNA into its host, the bacterium E. coli. Copies of the the viral DNA are made by E. coli's own enzymes. In addition RNA polymerase transcribes

viral m-RNA, which in turn is used to produce viral proteins that are used in the assembly of new T4 phages. One of these proteins can actually hydrolyse the DNA of E. coli, producing the building blocks for the phage's own DNA. Once the new phages are assembled another phage protein is capable of lysing the E. coli cell from the inside and the viral copies are released and the entire process can start over. Phages that reproduce via the lytic cycle are called virulent viruses
Lysogenic Cycle : Not all phage infections result in immediated cell lysis. After injection of the phage DNA, it is possible that the phage DNA (through insertion sequences) becomes incorporated in the host's DNA. In this stage the host can undergo many cellular divisions and continue with its normal metabolism. However, occationally the viral DNA can be excised from the host's DNA and a lytic cycle begins. These events are relatively rare and are initiated by uv light or chemials. As a result of lysogeny an organism can exhibit new properties. For example the toxin of Corynebacterium diphtheria which causes diphtheria, is only produced by organisms that are infected by a phage, since only the phage DNA codes for the toxin. Certain animal viruses undergo a very similar process to lysogeny. After infection they can remain silent for long periods of time before they become virulent.
Lifecycle of DNA or RNA viruses
The virus with its protein studded envelope makes contact with glycoprotein receptors on the surface of the host cell. The entire virus can enter the host cell by endocytosis (image)
. Alternatively, the enveloped virus fuses the viral membrane with the host membrane and capsid proteins and DNA (RNA) are released into the cytoplasm of the host, while the viral envelope remains incorporated in the cellular membrane. The viral DNA is replicated by the cellular enzymes and the viral genes are transcripted by the hosts RNA polymerase. New capsid proteins and components of the envelope are synthesized. The glycoproteins of the envelope are assembled on the inside of a transitionary vesicle which is released from the Golgi and subesquently fuses with the plasma membrane of the host.
The capsid with viral DNA will associate with the viral section of the plasma membrane and the now assembled virus will bud from the host cell.
RNA viruses
RNA viruses contain genomic RNA instead of DNA. There are a number of different ways in which RNA viruses replicate. (-) = antisense RNA, (+) = sense RNA
 Viral ss RNA (+)
A (-) strand is transcribed from the (+) strand by a viral RNA dependent RNA polymerase and a m-RNA is transcribed from the (-) strand. The m-RMA codes for capsid and other proteins. Capsid and ssRNA(+) strand form the new virus.

The polio virus replicated by this mechanism
Viral ss RNA (+)
A (-) strand is transcribed from the (+) strand by a viral RNA dependent RNA polymerase. A long strand and a short strand of m-RNA is transcribed from the (-) strand. The long m-RNA codes for capsid proteins, the short one codes for

envelope proteins. A new virus is assembled, the long m-RNA can be incorporated as viral RNA. The encephalitis virus replicated by this mechanism
 Viral ss RNA (-)
A (+) strand is transcribed from the (-) strand by a viral RNA dependent RNA polymerase. The (+) strand seves as a m-RNA which codes for viral proteins. The m-RNA is transcribed to yield more (-) strands that are incorporated into the new viruses as viral ss RNA (-). The rabies virus replicated by this mechanism
 Viral ds RNA (+)and (-)
A m-RNA or (-) strand is produced inside the capsid and released into the cytoplasm of the host cell. Viral proteins are synthesized and (+) and (-) strands combine to dsRNA to be incorporated into the new viruses . The Colorado tick fever virus replicated by this mechanism
 Retroviruses
A special group of RNA viruses are called retroviruses and are only found in eukaryotic cells. Retro refers to the reverse flow of genetic information from
RNA to DNA. All the genetic information of the virus is stored in RNA rather than in DNA . Retroviruses have an enzyme called reverse transcriptase, which is encoded in their RNA. After infection the reverse transcriptase makes a complementary DNA copy (cDNA) of the viral RNA. A complementary copy of the cDNA strand is synthesized by the enzymes of the host cell. It can enter the nucleus, where it is inserted in the host DNA assuming a latent form. Virulence begins if the inserted viral DNA transcript is excised, transcribed into m-RNA and with the aid of the cellular enzyme machinery viral proteins are expressed. This allows new viruses to be assembled which can bud from the host cell and infect other cells.
Influenza virus ( Fig. 13.4 ). The flu virus consists of eight ssRNA(-) segments incased in a capsid, which is surrounded by an envelope (lipid biayer) which is studded with two types of glycoproteins, Hemaglutinin (H) and Neuraminidase (N) image . The viral RNA does not act itself as m-RNA. The virus has a specific RNA polymerase which transcribes m-RNAs from each of the viral RNA segments. Some m-RNAs can be read in different reading frames, producing two different proteins. If the virus specific RNA polymerase is missing, the virus is not infectious. Hemaglutinin on the lipid layer surface of the virus attaches to receptors on the host cell. This allows the virus to enter the host cell. Neuraminidase can lyse the host cell from the inside allowing the newly assembled viruses to leave the cell The transcription process is not very accurate, thus both hemaglutinin (H) and neuraminidase (N) can change their structure. Antibodies against the virus are mainly directed against H and N, however antibodies against H are more important in the defense against the virus. Depending on the type of H and N the influenza virus is classified into antigenic types. The Asian flu 1957 was designated
H
2
N
2
. The virus was formed by recombination of human and duck influenza viruses.
Over 50 million individuals were infected and 70,000 died in USA. The killer flu in 1918 killed 22 million people world wide . The Hong Kong flu in 1968 was designated H
3
N
2
,
34,000 died in the USA. It is not possible to develop a vaccine that provides long term

protection, since each new strain of the virus has be identified in time before a vaccine can be made. Using information from China, Taiwan and Japan annual vaccines are developed by the CDC. These vaccines are usually multivalent, defending against different strains of the virus.
Mumps virus
The make up of the virus and its replication mechanism are very similar to the above discussed influenza virus with the exception that its RNA is not segmented but consits of one single stranded RNA. Mumps causes swelling of the parotid gland (located below the ear) . The virus is present in saliva and secretions of the respiratory tract. The measels virus belongs to the same class as the mumps virus.
Poliomyelitis virus
The polio virus contains a single strand of genomic RNA, which identical to the viral m-
RNA. During replication a complementary copy of the genomic RNA is synthesized, which serves as template for the synthesis of more genomic viral RNA. During translation of viral m-RNA a long polypeptide is generated, which is then cleaved into smaller fully functioning viral proteins. After initial infection of throat, and small intestine the virus enters the blood and may eventually enter the cells of the central nervous system, causing paralysis. Since the introduction of the Salk vaccine in 1954 the incidents of polio have dramatically reduce.
Hepatitis
Viral hepatitis is the inflammation of the liver. There are various forms of viral hepatitis.
The hepatitis A virus consists of a single stranded RNA embedded in a capsid with no envelope. The virus causes loss of appetide, nausia, fever, chills and possibly jaundice , however no chronic liver infections.
The hepatitis B virus has a double stranded DNA, envelope. It does not replicate its DNA directly but uses an RNA intermediate for its replication (similar to retroviruses as we will see later). This virus has an incubation period of 4-26 weeks and causes chronic liver diseases
The hepatitis C virus has single stranded RNA and an envelope. In 50% of the cases, the liver infection is chronic.
The hepatitis D virus has single stranded RNA and an envelope. The virus is highly virulent with the highest death rate.
Rhinovirus
About 50% of the common colds are caused by the rhinovirus, approxinately 10 % are caused by coronaviruses and in 40% of cold cases no agent has been identified. Most cold viruses use only two receptors on the nasal mucosa. A single virus is often enough to cause a cold.
Rabies
The rabies virus has a single stranded RNA. The disease has a long incubation period and results initially in mild symptoms (muscle spasms). If not treated nerve cell and the sinal cord are affected causing death

Human Immunodeficiency Virus (HIV) HIV geogr. distr. HIV
HIV is the virus that causes Acquired Immunodeficiency Syndrome (AIDS). AIDS was first reported in USA in 1981. The virus was most likely into humans from mokeys
(African green monkey). Affected individuals have no resistance to infections, they die of diseases which healthy individuals can easily fight off. The risk of infection through day to day contacts with infected individuals is very low. The virus resides in body fluids such as blood, semen and vaginal fluids.
HIV, a retrovirus has two RNA strands each associated with a reverse transcriptase. The
RNA is surrounded by capsid proteins which in turn are embedded in an envelope. The envelope is studded with a glycoprotein (gp120) which can bind to the CD4 MHC protein on human T-helper cells. Thus, HIV infects a leukocyte which is very important in the immune response. The reproductive cycle of HIV is shown below
Treatments of AIDS includes the development of vaccines which can prevent HIV from binding to the CD4 receptor. AZT (ddI or ddC) inhibit the reverse transcriptase and protease inibitors shut down the enzyme protease , which is necessary to assemble the virus.