Chapter 25HIV

Viruses

• Viruses are small, subcellular agents - 100 nanometers in diameter.

– estimated to be over 10 million virus particles in every milliliter of sea water!

• These microorganisms are unable to multiply outside a host cell, and therefore, are classified as intracellular, obligate parasites

• They have only one type of nucleic acid (RNA or DNA), which can be single-stranded or double-stranded

• The simplest viruses are only comprised of nucleic acid and a protein coat

Viruses

• Nucleic acid – Either DNA or RNA (Single or double

stranded)– Contains the genetic

information that controls what the virus will have (as far as proteins, nucleic acid, etc)

– Controls the machinery of the host cell to support viral replication

• Protein coat (Capsid)– Gives the virus strurcture– Protects the nucleic acid

from extracellular environmental insults such as proteases and nucleases

– Permits the attachment of the virion to the membrane of the host cell.

Some may also have an envelope (lipid)– may contain “spikes that aid in attachment (Derived when leaving cell)

http://www.niaid.nih.gov/factsheets/howhiv.htm#pathogenesis

• Viral genome – penetrates and infects host cell – virus replication mainly depends on host cell

machinery for energy and synthetic requirements

• Virion components – are synthesized separately within the cell – then assembled to form progeny particles.

This assembly-type of replication is unique to viruses

Replication of Viruses

• Most often causes some type of cell damage or death

– Many viruses existence within the host at a low enough level that the host is not aware of this

– Since the viruses’ survival depends entirely on the host, most viruses tend to cause mild infections

• Death in the host = death of the virus – this is not the usual mode of action for most viruses

because their existence would cease to be

• Exceptions human immunodeficiency virus, ebola virus, pandemic influenza

Extreme Dependence on Host cell

• Distinctive of viruses – many have specificities to the species they can infect

• Virus must grow within a host cell• Specific conditions for their growth

– An example - rhinovirus which requires the temperature of its environment not to exceed 340 C

– Therefore, this places a restriction to their growth to only cells in cool outer layer of the nasal mucosa

– This also prevents the virus from spreading to deeper cells where the temperature is higher

• An intracellular location protects a virus from some of the host immune defenses

– It also makes them difficult targets for chemotherapy

• Virus lives within the human cell and uses the host cell machinery

– this makes host-directed processes and viral-directed processes similar

This makes it difficult to design drugs that will only go after a viral-infected human cell and not also an uninfected human cell

HIV is a RetrovirusFamily Retroviridae

• Enveloped RNA viruses

• RNA viruses that convert RNA to DNA – Reverse transcriptase– Integration into human DNA genome– Occur in two forms

• Can be in a “resting form” which doesn’t cause destruction of the host cell, or

• Active - cause replication and destruction of cell

Retrovirus

• Reverse transcriptase attached to the viral RNA molecules.

• Reverse transcriptase synthesizes DNA copies of the RNA.

• DNA enters the nucleus • inserted into the DNA of the host. • Transcription by the host's enzymes into RNA• New RNA

– Translation to viral genes– Incorporated into fresh virus particles

http://www.niaid.nih.gov/factsheets/howhiv.htm#pathogenesis

• HIV has 9 genes (> 500 genes in a bacterium, and ~ 20,000-25,000 in a human) – 3 genes (gag, pol and env)

• Code for structural proteins for new virus particles

– 6 other genes (known as tat, rev, nef, vif, vpr and vpu)

• Code for proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease

HIV Transmission

• Sexual Transmission

• Blood Transmission

• Mother to Child

Laboratory Testing for HIV

• Once infected, it takes between 3-6 months for enough antibodies to be formed for screening tests to be positive

• If testing is negative, a person should:– Be retested in 6 months – Engage in no risky behavior during that time

• If results are negative at that time, one can consider that they are not infected

From HIV Infection to AIDS

• First symptoms after infection may mimic the flu

• No other symptoms may occur until enough CD4 cells have been destroyed by HIV – With loss of CD4 cells, the immune system

cannot protect– When CD4 count reaches 200 – person

considered to have AIDS

From HIV Infection to AIDS

• Without therapy, the time from infection to AIDS = approximately 8-10 years

• Antiretroviral therapy can prolong this time span

• Some people naturally have not progressed from HIV infection to AIDS– Referred to as long-term nonprogressors