Comprehensive Virus Structure, Classification, and Replication Methods

Obligatory intracellular parasites

Cannot replicate outside host cells

Contain DNA OR RNA

NEVER BOTH

Protein coat

Present in viruses

Host Range

Spectrum of host cells a virus can infect

Bacteriophages

Viruses that infect bacteria

Size range of viruses

20 nm to 1000 nm in length

Virion

Complete, fully developed viral particle

Nucleic Acid

DNA or RNA (never both), can be single- or double-stranded, can be linear or circular

Capsid

Protein coat made of capsomeres (subunits)

Envelope

Lipid, protein, and carbohydrate coating (only on some viruses)

Spikes

Projections from outer surface of some viruses

Helical viruses

Hollow, cylindrical capsid

Polyhedral viruses

Many-sided viruses

Enveloped helical virus

Example: Influenza

Enveloped polyhedral virus

Example: Herpes virus

Complex viruses

Complicated structures

Taxonomy of Viruses

Grouped based on genomics and structure

Genus names

End in: -virus

Family names

End in: -viridae

Order names

End in: -ales

Viral species

Group of viruses sharing same genetic information and ecological niche

Subspecies designation

Designated by number (e.g., HIV-1, HIV-2)

Plaques

Clearings on bacterial lawn on agar surface formed by bacteriophages

Plaque-forming units (PFU)

Each plaque equals one initial virus

Cytopathic Effect (CPE)

Deterioration of virally infected cells

Western blotting

Reaction of virus with antibodies

RFLPs

Restriction Fragment Length Polymorphisms

PCR

Polymerase Chain Reaction

Viruses attach to cell membrane

Target: proteins and glycoproteins on plasma membrane that are hijacked by virus

Entry

Receptor-mediated endocytosis OR fusion

Uncoating

By viral or host enzymes

Eclipse period

Occurs during uncoating

Ways coats are removed

Host lysosomal enzymes, Enzymes encoded by viral DNA, Lower pH in vesicles

Biosynthesis

Production of nucleic acid and proteins

Maturation

Nucleic acid and capsid proteins assemble

Release

By budding (enveloped viruses) - cell usually doesn't die; By rupture (non-enveloped viruses) - usually results in death

DNA viruses replicate

DNA in nucleus using viral enzymes

Capsid synthesis

In cytoplasm using host cell enzymes

Virions formation

Capsid proteins move to nucleus and join with newly synthesized DNA

Adenoviridae

Double-stranded DNA, nonenveloped; Respiratory infections in humans; Tumors in animals

Herpesviridae

Double-stranded DNA, enveloped; 100 herpesviruses total

HHV-1 and HHV-2

Simplexvirus: cold sores

HHV-3

Varicellovirus: chickenpox

HHV-4

Lymphocryptovirus: mononucleosis

HHV-5

Cytomegalovirus

RNA virus characteristics

Virus RNA multiplies in cytoplasm; Uses RNA-dependent RNA polymerase (RDRP) synthesized by host cell from viral genes

ssRNA; + (sense) strand

Viral RNA serves as mRNA for protein synthesis; Translated to two principal proteins

ssRNA; - (antisense) strand

Serves as template for more + strands

Retrovirus

Converts RNA to DNA

Retroviridae

Family of retroviruses including Lentivirus: HIV and Oncoviruses

Retrovirus multiplication steps

Retrovirus enters by fusion; Uncoating releases two viral RNA strands and viral enzymes; Reverse transcriptase copies viral RNA

Latent Virus

Remains in asymptomatic host cell for long periods

Examples of Latent Virus

Cold sores (Simplexvirus), Shingles (Varicellovirus)

Persistent Viral Infection

Occurs gradually over long period

Example of Persistent Viral Infection

HIV

Global HIV Statistics (2016)

36.7 million people globally living with HIV

HIV in Eastern and Southern Africa

19.4 million in Eastern and Southern Africa

HIV in the United States

1.2 million HIV patients

HIV Awareness in the US

1 in 8 unaware of status

African Americans and HIV (2014)

44% of people living with HIV

HIV Survival Times

HIV survives 6 hours outside a cell

Routes of HIV Transmission

Intimate sexual contact, Breast milk, Transplacental infection, Contaminated needles, Organ transplants, Blood transfusion

Most Dangerous Form of Sexual Contact

Anal-receptive intercourse

HIV-1

Related to viruses that infect chimpanzees and gorillas

Group M of HIV-1

Accounts for 90% of HIV-1 cases

HIV-2

Related to viruses that infect monkeys and sooty mangabeys

Pathogenicity of HIV-2

Less pathogenic than HIV-1

HIV Predecessor

1625

Earliest Reports of HIV

1920

Zoonotic Transmission of HIV

Chimpanzee to human, possibly through bushmeat

Geographic Spread of HIV

Democratic Republic of Congo → Central Africa → East Africa → South Africa → Haiti → USA (New York, SF)

What is HIV?

Lentivirus

A type of virus that includes HIV.

Phospholipid envelope

A membrane surrounding the virus.

Glycoproteins: gp120 and gp41

Proteins on the virus surface that facilitate entry into host cells.

2 identical strands of RNA

The genetic material of the virus.

Reverse Transcriptase

An enzyme that converts viral RNA into DNA.

T Cells

A type of immune cell infected by HIV.

Macrophages, Monocytes, Microglia

Types of immune cells that can be infected by HIV.

Dendritic cells

Immune cells that can be infected by HIV.

Astrocytes

Brain cells that may be infected by HIV.

CD4 (primary receptor)

The main receptor HIV uses to enter host cells.

Co-receptors: CCR5 or CXCR4

Additional receptors that HIV uses to infect cells.

Phase 1: Asymptomatic or Lymphadenopathy

The initial infection stage of HIV.

Phase 2: CD4+ T Cell Decline

Stage where CD4+ T cells decline steadily.

Phase 3: AIDS

Stage where CD4+ count falls below 200 cells/μl.

Latently Infected Macrophage

A macrophage where HIV persists as provirus or complete virion.

Activated Macrophage

A macrophage that produces new viruses from provirus.

Use of condoms

A method of preventing HIV transmission.

Pre-exposure prophylaxis (PrEP)

A medication strategy to prevent HIV infection.

Entry inhibitors: Maraviroc

A drug that blocks receptors on host cells that bind HIV.

Reverse Transcriptase Inhibitors

Drugs that inhibit the reverse transcriptase enzyme.

Integrase Inhibitors

Drugs that inhibit viral DNA integration into the host genome.

HIV-Associated Neurocognitive Disorders

Cognitive impairments associated with HIV infection.

Natural Penicillins

Penicillins derived from natural sources.

Penicillin G

Administered IV or IM; mnemonic 'Gun (needle)'.

Penicillin V

Oral penicillin; mnemonic 'Vitamin taken by mouth'.

Semisynthetic Penicillins

Modified penicillins to enhance effectiveness.

Penicillinase-Resistant

Penicillins resistant to penicillinase.

Methicillin

Discontinued in the US due to MRSA.