Viruses (Ch. 11, Lec. 17)
Tuesday, November 17, 2020 9:29 PM
• DNA VIRUSES Ex. Chicken pox, shingles, skin infections.
11.5: Herpes Simplex Virus--dsDNA virus (I)
• HSV has 2 main strains: HSV-1 (oral lesions) and HSV-2 (genital lesions).
• HSV primary infection is epithelial, however latent infection can occur within neurons of ganglia.
• No cure, prevention for future outbreaks.
• HSV-1 genome is 152kB, larger than most; encodes >70 genes.
• HSV-1 replication is similar to lytic cycle phages; prophages are integrated and encoded in to the genome, then activated at a later time.
• Ex. Varicella Zoster Virus (dsDNA herpesvirus)
○ Chickenpox: recovery from chickenpox provides immunity, but does not eliminate the virus ->
○ Remains latent in cranial nerves/sensory neurons in dorsal root ganglia.
○ Shingles: reactivated form of chickenpox.
○ Pain persists after rash/blisters; also needs acyclovir treatment.
• RNA VIRUSES Ex. SARS-Cov-2 (IV), Zika.
• (+) RNA viruses must carry RdRp b/c the (+) RNA is not recognized by the host cell. Ex. Picornavirus
1. Viral (+) RNA genome is inserted into the host cytoplasm.
2. Viral (+) RNA is translated to make RNA-dependent RNA polymerase (RdRp).
3. RdRp uses the picornavirus RNA template to make (-) strand RNA; serves as a template for other viral mRNAs.
4. Progeny genomic RNA is replicated in virus-induced vesicles from the ER.
• Ex. SARS-CoV-2 Remdesivir is able to inhibit RdRp; SARS-CoV-2 cannot function when medication is present.
• Pfizer-BioNTech vaccine is in the form of mRNA; stored at -75C.
○ Lipid nanoparticles encloses mRNA that encodes the viral spike proteins.
• Ex. Zika. Another (+) RNA virus.
○ Caused birth defects to pregnant women who are infected; major problem in 2018.
• -> (-) VIRUSES AKA Strands that are complementary to the (+) virus strands.
• *(+) strands are needed to synthesize viral proteins!*
• Can form complimentary (+) strands -> make (-) strand RNA as the viral genome when making progeny.
•
• Ex. Influenza virus. (-) strand RNA (V), SEGMENTED
○ How are the flu and cold different?
• Flu is caused by the influenza virus, (-) strand RNA virus.
• Cold is usually caused by rhino/coronavirus, (+) strand RNA virus.
○ Flu virus contains 2 types of of S proteins: Hemagglutinin(HA) and Neuraminidase(NA).
• Hemagglutinin binds to sialic acids on host cell.
• Neuraminidase releases virion once they've reproduced. (Budding)
○ HA: defines viral tropism, major surface epitope seen by immune system.
○ Influenza has a HI freq of genetic changes:
• Antigenic drift: accumulation of point mutations -> a.a. substitutions.
• Antigenic shift: genetic re-assortment of different viral flu strains. (Viruses infect the same cell and are incorporated into a new
capsid.)
• Re-assortment created H1N1! New viral segments can lead to new (S) proteins.
○ Antivirals: inhibit NA. NA inhibitors will block virions from being released. -> Reduces symptoms to 1d.
• RETROVIRUSES Ex. HIV
• (+) RNA is reverse transcribed into (-) DNA -> dsDNA intermediate integrates into host genome AND serves as a template for mRNA
synthesis and genomic RNA.
• Ex. HIV. (+) strand RNA (IV)
○ Sequence comparison has shown that the immunodeficiency virus has entered the human pop more than once, from Simian IV strains
derived from related primates in Africa. (Evolved from monkey viruses that have combined w/ human DNA.)
○ (+) sense, ssRNA RETROVIRUS. Enveloped retrovirus = RNA genome is copied into DNA and integrated into the host genome.
○ (HIV entry and pathogenicity) 1. Viral gp120 and gp41 proteins bind to CD4 and co-receptor CCR5 or (CXCR4).
2. HIV can infect CD4+ T cells AND macrophages/dendritic cells (DC).
3. Leads to viral lysis of infected cells, INCed apoptosis, killing by CD8+ T cells. May also disable DCs.
○ Mutates rapidly-- evades immune system AND confers resistance to anti-viral drugs.
○ HIV Reverse transcriptase is a "sloppy bitch!" high mutation rate -> difficult to develop a vaccine.
Tuesday, November 17, 2020 9:29 PM
• DNA VIRUSES Ex. Chicken pox, shingles, skin infections.
11.5: Herpes Simplex Virus--dsDNA virus (I)
• HSV has 2 main strains: HSV-1 (oral lesions) and HSV-2 (genital lesions).
• HSV primary infection is epithelial, however latent infection can occur within neurons of ganglia.
• No cure, prevention for future outbreaks.
• HSV-1 genome is 152kB, larger than most; encodes >70 genes.
• HSV-1 replication is similar to lytic cycle phages; prophages are integrated and encoded in to the genome, then activated at a later time.
• Ex. Varicella Zoster Virus (dsDNA herpesvirus)
○ Chickenpox: recovery from chickenpox provides immunity, but does not eliminate the virus ->
○ Remains latent in cranial nerves/sensory neurons in dorsal root ganglia.
○ Shingles: reactivated form of chickenpox.
○ Pain persists after rash/blisters; also needs acyclovir treatment.
• RNA VIRUSES Ex. SARS-Cov-2 (IV), Zika.
• (+) RNA viruses must carry RdRp b/c the (+) RNA is not recognized by the host cell. Ex. Picornavirus
1. Viral (+) RNA genome is inserted into the host cytoplasm.
2. Viral (+) RNA is translated to make RNA-dependent RNA polymerase (RdRp).
3. RdRp uses the picornavirus RNA template to make (-) strand RNA; serves as a template for other viral mRNAs.
4. Progeny genomic RNA is replicated in virus-induced vesicles from the ER.
• Ex. SARS-CoV-2 Remdesivir is able to inhibit RdRp; SARS-CoV-2 cannot function when medication is present.
• Pfizer-BioNTech vaccine is in the form of mRNA; stored at -75C.
○ Lipid nanoparticles encloses mRNA that encodes the viral spike proteins.
• Ex. Zika. Another (+) RNA virus.
○ Caused birth defects to pregnant women who are infected; major problem in 2018.
• -> (-) VIRUSES AKA Strands that are complementary to the (+) virus strands.
• *(+) strands are needed to synthesize viral proteins!*
• Can form complimentary (+) strands -> make (-) strand RNA as the viral genome when making progeny.
•
• Ex. Influenza virus. (-) strand RNA (V), SEGMENTED
○ How are the flu and cold different?
• Flu is caused by the influenza virus, (-) strand RNA virus.
• Cold is usually caused by rhino/coronavirus, (+) strand RNA virus.
○ Flu virus contains 2 types of of S proteins: Hemagglutinin(HA) and Neuraminidase(NA).
• Hemagglutinin binds to sialic acids on host cell.
• Neuraminidase releases virion once they've reproduced. (Budding)
○ HA: defines viral tropism, major surface epitope seen by immune system.
○ Influenza has a HI freq of genetic changes:
• Antigenic drift: accumulation of point mutations -> a.a. substitutions.
• Antigenic shift: genetic re-assortment of different viral flu strains. (Viruses infect the same cell and are incorporated into a new
capsid.)
• Re-assortment created H1N1! New viral segments can lead to new (S) proteins.
○ Antivirals: inhibit NA. NA inhibitors will block virions from being released. -> Reduces symptoms to 1d.
• RETROVIRUSES Ex. HIV
• (+) RNA is reverse transcribed into (-) DNA -> dsDNA intermediate integrates into host genome AND serves as a template for mRNA
synthesis and genomic RNA.
• Ex. HIV. (+) strand RNA (IV)
○ Sequence comparison has shown that the immunodeficiency virus has entered the human pop more than once, from Simian IV strains
derived from related primates in Africa. (Evolved from monkey viruses that have combined w/ human DNA.)
○ (+) sense, ssRNA RETROVIRUS. Enveloped retrovirus = RNA genome is copied into DNA and integrated into the host genome.
○ (HIV entry and pathogenicity) 1. Viral gp120 and gp41 proteins bind to CD4 and co-receptor CCR5 or (CXCR4).
2. HIV can infect CD4+ T cells AND macrophages/dendritic cells (DC).
3. Leads to viral lysis of infected cells, INCed apoptosis, killing by CD8+ T cells. May also disable DCs.
○ Mutates rapidly-- evades immune system AND confers resistance to anti-viral drugs.
○ HIV Reverse transcriptase is a "sloppy bitch!" high mutation rate -> difficult to develop a vaccine.
