The Influenza Virus Hemagglutinin (HA) spikes used for attachment to host cells Neuraminidase (NA) spikes used to release virus from cell INFLUENZA ANIMATION Figure 24.15

The Influenza Virus Antigenic shift Antigenic drift Changes in HA and NA spikes Probably due to genetic recombination between different strains infecting the same cell Antigenic drift Point mutations in genes encoding HA or NA spikes May involve only 1 amino acid Allows virus to avoid host cell antibodies ANTIGENTIC SHIFT ANIMATION

Influenza Serotypes Type Antigenic Subtype Year Severity Common Name A H3N2 H1N1 H2N2 H5N1 1889 1918 1957 1968 2004 2009 Moderate Severe Low Spanish Flu Asian Flu Hong Kong Flu Bird Flu Swine Flu Hemagglutinin types = H1 –H17 Neuraminidase types = N1-N9

DNA Viruses Adenovirus – acute respiratory infections like the common cold Poxvirus - cowpox, smallpox Herpesvirus – 100 herpesviruses are known! Ex: HHV-1 and HHV-2 Simplexvirus – coldsores, HHV-3 – chickenpox and HHV-4 – mono Papovavirus – warts. Some of these species are capable of causing cancer.

Viruses General Life Cycle: Virus Replication Viruses General Life Cycle: Attachment Penetration/entry Biosynthesis Assembly/Maturation Release Bacterial Viruses (phages) Animal Viruses Transduction – when phage packages - it occasionally brings piece of host DNA with it. Lytic Lysogenic Lysogen – a latently infected bacteria cell Lysogenic Phages – a latent virus Phage (short for bacteria phage) – virus that infects bacteria. Plaques replication Transduction – when an error is made and package’s host DNA instead! – Usually random event Non-infectious Cell metabolism SLOWS OR STOPS Host Cell Dies Prophage – virus has incorporated it’s DNA into bacteria’s DNA

Multiplication of Animal Viruses Attachment: Viruses attach to cell membrane Penetration by endocytosis or fusion Uncoating by viral or host enzymes Biosynthesis: Production of nucleic acid and proteins Maturation: Nucleic acid and capsid proteins assemble Release by budding (enveloped viruses) or rupture

Attachment, Penetration, Uncoating By pinocytosis Figure 13.14a

Attachment, Penetration, Uncoating By fusion Figure 13.14b

Multiplication of DNA Virus Figure 13.15

RNA Viruses ssRNA: + strand Picornovirus – polio Smallest viruses Togavirus – arthropod-borne arboviruses Enveloped (toga) ssRNA: - strand Rhabdovirus – rabies Bullet shaped Retrovirus Lentivirus – HIV which cause AIDS

Sense Strand (+ Strand) RNA Virus Figure 13.17a

Antisense Strand (– Strand) RNA Virus Figure 13.17b

Double-Stranded RNA Virus Figure 13.17c

Multiplication of RNA-Containing Viruses Figure 13.17

Multiplication of a Retrovirus Figure 13.19

Viral escape – presence or absence of envelope Two methods by which mature viruses escape their host cell 1. Host cell lysis - releases naked or non-enveloped viruses 2. Budding – virus passes through cell membrane – takes part of host cell’s membrane – envelope is formed around capsid

Budding of an Enveloped Virus Figure 13.20

Budding of an Enveloped Virus Figure 13.20

Growing Animal Viruses Animal viruses may be grown in living animals or in embryonated eggs Figure 13.7

Bacteriophages

Figure 13.6 The complex shape of bacteriophage T4. Bacteriophages (Phages) Figure 13.6 The complex shape of bacteriophage T4. Head Tail fibers Tail Base plate

A Viral One-Step Growth Curve Figure 13.10

The Lytic Cycle Attachment: Phage attaches by tail fibers to host cell Penetration: Phage lysozyme opens cell wall; tail sheath contracts to force tail core and DNA into cell Biosynthesis: Production of phage DNA and proteins Maturation: Assembly of phage particles Release: Phage lysozyme breaks cell wall

Lytic Cycle of a T-Even Bacteriophage 1 2 3 Figure 13.11

The Lytic Cycle The lytic cycle is a phage reproductive cycle that culminates in the death of the host cell The lytic cycle produces new phages and digests the host’s cell wall, releasing the progeny viruses A phage that reproduces only by the lytic cycle is called a virulent phage Bacteria have defenses against phages, including restriction enzymes that recognize and cut up certain phage DNA

Lytic Cycle of a T-Even Bacteriophage 4 Figure 13.11

Figure 13.8 The lytic replication cycle in bacteriophages.

Figure 13.9 Pattern of virion abundance in lytic cycle. The Lytic Cycle Progression Figure 13.9 Pattern of virion abundance in lytic cycle.

Growing Lytic Viruses Viruses must be grown in living cells Bacteriophages form plaques on a lawn of bacteria Figure 13.6

Results of Multiplication of Bacteriophages Lytic cycle Phage causes lysis and death of host cell Can lead to Generalized transduction Lysogenic cycle Prophage DNA incorporated in host DNA Phage conversion Can lead to Specialized transduction

The Lysogenic Cycle The lysogenic cycle replicates the phage genome without destroying the host The viral DNA molecule is incorporated into the host cell’s chromosome This integrated viral DNA is known as a prophage Every time the host divides, it copies the phage DNA and passes the copies to daughter cells

The Lysogenic Cycle An environmental signal can trigger the virus genome to exit the bacterial chromosome and switch to the lytic mode Phages that use both the lytic and lysogenic cycles are called temperate phages

The Lysogenic Cycle Figure 13.12

Generalized Transduction 2 3 4 5 6 Figure 8.28

Generalized Transduction 2 3 4 5 6 Figure 8.28

Specialized Transduction Figure 13.13

Specialized Transduction Figure 13.13

Viruses General Life Cycle: Viral Replication Viruses General Life Cycle: Attachment Penetration/entry Biosynthesis Maturation Release Bacterial Viruses (phages) Animal Viruses Transduction – when phage packages - it occasionally brings piece of host DNA with it. Lytic Lysogenic Lysogen – a latently infected bacteria cell Lysogenic Phages – a latent virus Phage (short for bacteria phage) – virus that infects bacteria. Plaques replication Transduction – when an error is made and package’s host DNA instead! – Usually random event Non-infectious Cell metabolism SLOWS OR STOPS Host Cell Dies Prophage – virus has incorporated it’s DNA into bacteria’s DNA

hIV HUMAN IMMUNODEFICIENCY VIRUS

AIDS 1981: In United States, cluster of pneumonia and Kaposi's sarcoma (cancer of skin & blood vessels) discovered in young homosexual men The men showed loss of immune function 1983: Discovery of virus causing loss of immune function – HIV

The Origin of AIDS Crossed the species barrier (from chimps & monkeys) into humans in Africa in the 1930s through animal butchering for food Patient who died in 1959 in Congo is the oldest known case Spread in Africa as a result of urbanization Spread worldwide through modern transportation and unsafe sexual practices

HIV Transmission HIV survives 6 hours outside a cell HIV survives less than 1.5 days inside a cell Infected body fluids transmit HIV via Sexual contact Breast milk Transplacental infection of fetus Blood-contaminated needles Organ transplants Artificial insemination Blood transfusion

Structure of HIV and Infection of CD4+ Cell Figure 19.13

HIV Attachment Figure 19.13

Fusion of the HIV w/Cell HIV Entry Figure 19.13 Figure 19.13

HIV Infection http://www.johnkyrk.com/virus.html Figure 13.19

Active HIV Infection in CD4+ T Cells Latent virus http://www.galaxygoo.org/biochem/hiv/hiv_lifecycle.html Figure 19.14b

Active HIV Infection in Macrophages Figure 19.15b

Latent HIV Infection in Macrophages Figure 19.15a

Vaccine Difficulties Why?

Vaccine Difficulties Mutations – retroviruses mutate more often than DNA viruses. Why? Hint: compare enzymes involved. Antibody-binding sites “hidden” when viruses are latent

The Progression of HIV Infection Figure 19.16

Worldwide Distribution of AIDS and HIV 14,000 new cases worldwide per day! Figure 19.17

Chemotherapy reverse transcriptase inhibitors Protease inhibitors Fusion inhibitors HAART – highly active antiretroviral therapy Combination of drugs to counteract drug mutations Cannot eliminate latent viruses; goal is to reduce viral load to level that immune system can handle http://pharmaxchange.info/press/2011/01/hiv-life-cycle/ http://www.pbs.org/wgbh/evolution/library/10/4/l_104_06.html http://www.pbs.org/wgbh/evolution/library/10/4/l_104_05.html

What antivirals did you find???

Other Ideas Lactobacillis in vaginal microbiota that can produce bacteriocins that inhibit HIV Virus decoys – HIV binds decoy instead of CD4 Boosting immunity – hormone to increase CD4 cells