Viral Genomes, Capsids, and Infection Stages

• Viral genomes are the genetic material of a virus and can be either single or double-stranded DNA or RNA, but not both.
• Viral genomes code for the synthesis of viral components and viral enzymes needed for replication.
• Capsids are protein shells that surround and protect the viral genome and introduce it into host cells.
• Attachment proteins project from the capsid to aid in this process.
• Envelopes surround some animal viruses and are derived from the host cell's nuclear membrane, vacuolar membranes, or outer cytoplasmic membrane.
• Virus-encoded proteins, appearing as glycoprotein spikes, are incorporated into the envelope and facilitate attachment to host cell receptors.

Stages of Viral Infection

• Prodromal or incubation period is the time between infection and detection of clinical features.
• Examples of incubation periods: influenza (1-2 days), herpes simplex (5-8 days), rubella (17-20 days), and AIDS (1-10 years).
• Viruses can enter cells through trauma, such as insect bites, or via mucous membranes of the respiratory and alimentary tracts.
• Replication within mucous membrane cells can directly cause disease, such as respiratory illnesses
• Viruses may use a staging post, like poliovirus in alimentary tract cells before moving to anterior horn cells.
• Latency occurs when specific host cell proteins needed to activate viral genes are lacking, preventing viral replication.
• During latency, the virus remains inside the infected cell avoiding humoral immunity.
• Activation of host cell DNA in response to extracellular stimuli can cause the synthesis of host cell proteins, activating viral genes and replication.
• Herpes viruses often become latent and can cause recurrent conditions like cold sores, shingles, and post-chicken pox.

Methods of Damage

• Type II hypersensitivity reactions, involving IgG and/or IgM, are a major cause of viral-induced cell lysis.
• Type IV allergic reactions, not involving antibodies, are the second most common mechanism of viral-induced cell lysis.
• Some viruses produce viral components that are toxic to the host cell
• Viruses can transform benign cells into malignant cells.
• Certain viruses can alter human immune responses by changing immune cell metabolism or causing immune cell lysis.
• Many viral species induce cytoplasmic and/or nuclear changes in host cells.

Viral Classification

• Morphology considerations include size, shape, and whether the virus is enveloped or non-enveloped.
• Physicochemical properties encompass molecular mass, buoyant density, pH, thermal stability, and ionic stability.
• Classification also considers the type of genome (RNA or DNA).
• Macromolecules refers to protein composition and function.
• Antigenic and biological properties (host range, transmission tropism, etc.) are also important for classification.

DNA Viruses vs RNA Viruses

• DNA viruses store genetic information as DNA, while RNA viruses store it as RNA.
• Most DNA viruses are double-stranded, while most RNA viruses are single-stranded
• DNA viruses replicate inside the host cell's nucleus while RNA viruses are transcribed and then replicated in the cytoplasm
• Viral DNA is first transcribed into RNA, then mRNA is translated into viral proteins
• RNA can bypass transcription during protein synthesis since they already contain RNA in the genome
• DNA viruses usually show accurate replication that is stable due to the lower mutation rate, whereas RNA viruses often show error-prone replication and are unstable due to the higher mutation rate
• Newly synthesized viral DNA is packed into a pre-formed capsid called procapsid. Newly-synthesized viral RNA is not packed in a procaspid
• DNA viruses include Baltimore classification Classes I, II, and VII
• RNA viruses include Baltimore classification Classes III, IV, V, and VI
• Examples of DNA viruses: Adenoviruses, Herpesviruses, Poxviruses, Parvoviruses, and Hepadnaviruses. Examples of RNA viruses: Reoviruses, Picornaviruses, Togaviruses, Rhabdoviruses, and Retroviruses.
• Smallpox, herpes, and chickenpox are diseases of DNA viruses while AIDS, Ebola hemorrhagic fever, SARS, and the common cold are some diseases of RNA viruses

Papillomavirus

• There are more than 150 types of HPV, and over 30 types are spread through sexual contact.
• HPV causes six types of cancer: cervical (91%), vulvar (69%), vaginal (75%), oropharyngeal (72%), anal (91%), and penile (63%).
• Low-risk HPV types include 6, 11, 42, 43 & 44 which are associated with genital warts or benign lesions, not cervical cancer.
• High-risk HPV types include 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 & 68. All types are isolated in cervical cancer.

Warts

• Common warts, foot warts (verrucae), flat warts, and periungual warts are all conditions caused by papillomaviruses.

Herpesvirus

• Herpes simplex virus (HSV) can cause blisters and sores on the skin, usually around the mouth, nose, genitals, or buttocks.
• HSV infections can periodically reappear.
• Sores may be painful and unsightly and, rarely, fatal for chronically ill people and newborn babies.
• Type 1 is transmitted by kissing, sharing eating utensils, or sharing towels.
• Type 1 commonly affects the lips, mouth, nose, chin, or cheeks shortly after exposure, with patients barely noticing symptoms.
• Most people get Type 2 infections through sexual contact with an infected person, affecting up to 20% of sexually active adults.

Varicella Zoster Virus

• Chickenpox is a viral infection that causes a blister-like rash on the skin and mucous membranes.
• Blisters itch and break, scabs form, and blisters develop a secondary bacterial infection
• Symptoms include fever, abdominal pain, or a vaguely sick feeling along with blisters
• Younger children often have milder symptoms and fewer blisters.
• Chickenpox is generally a mild illness, but is deadly in persons who have leukemia or other diseases that weaken the immune system
• After chickenpox, the virus lies dormant in nerve tissue and can re-infect in the form of shingles, a re-infection of the varicella zoster virus
• Shingles: a rash or blisters on the skin that may be associated with severe pain affecting 1 dermatome.
• it is most common in people >50 years, but anyone who has had chickenpox is at risk for developing shingles.
• Shingles are more common in immunosuppressed individuals
• If face is involved, complications can lead to problems with hearing and vision.
• PHN pain persists for months, sometimes years, after shingles has healed.

Epstein-Barr Virus

• EBV infection during adolescence / young adulthood causes infectious mononucleosis in 35% to 50% of cases.
• Symptoms are fever, sore throat, and swollen lymph glands
• Sometimes, a swollen spleen or liver involvement may develop.
• Rarely heart problems or involvement of the central nervous system occur, but this is rarely fatal.
• There is no drug with demonstrates antiviral effects.

Other Herpesviruses

• Cytomegalovirus (HHV-5)
• Hairy oral leukoplakia (EBV) - (HHV-4)
• Kaposi's sarcoma - (HHV-8)

Pox Virus

• Smallpox (variola) has now been eradicated.
• The last naturally occurring outbreak of smallpox was in Somalia on 26th October 1977.
• Poxviruses are the most complex of viruses, featuring double-stranded DNA and 2 envelopes.

Molluscum Contagiosum

• Common benign skin growth is caused by a viral infection of the epidermis.
• Similar to warts, the virus enters through breaks in the skin/hair follicles.
• Molluscum does not affect any internal organs.
• They are usually small, shiny, flesh-colored or pink, dome-shaped growths with a small indentation in the center.
• Lesions usually form in clusters on the skin of the chest, abdomen, arms, groin, or buttocks.

Retrovirus

• A retrovirus inserts a copy of its RNA genome into the DNA of a host cell, changing the host cell's genome.

Human Immunodeficiency Virus (HIV) & AIDS

• HIV is transmitted by blood and sexual contact fluids.
• AIDS causes a profound defect in cell-mediated immunity, leading to opportunistic infections.
• HIV is a unique type of RNA virus that replicates through a DNA intermediate via reverse transcriptase.
• HIV binds to the CD4 molecule on helper T-cells and replicates within them, destroying them and leading to a decline in their population.
• The incubation period is 1-10 years
• Initial symptoms manifest as acute fever, followed by years of symptom-free latency
• Symptoms include progressive weight loss, intermittent fever, lymphadenopathy, chronic diarrhoea, and opportunistic infections (PC, KS, CMV)
• Treatment includes AZT/triple therapy.
• HIV prevalence is globally increasing, mostly due to antiretroviral treatment.
• The main mode of HIV transmission in sub-Saharan Africa is heterosexual contact.
• Mother-to-child transmission rates are decreasing.
• Injection drug use is a major risk factor for HIV in Eastern Europe, Central Asia, N. Africa, & the Middle East.
• Men who have sex with men remain at the highest risk for infection in many countries of N. America, Western Europe, and Oceania.

Picornavirus

• Several human enteroviruses primarily spread by the faecal-oral route, e.g., sewage contamination, poor sanitation, etc.

Poliomyelitis

• Poliomyelitis may be sub-clinical with none or very mild symptoms, e.g., slight fever, headache, sore throat.
• Non-paralytic cases last 1-2 weeks, showing fever, headache, vomiting, rash, and muscle stiffness.
• Paralytic cases result in the destruction of the anterior horn cell of the spinal cord; symptoms include fever, loss of extensor response, bloating, muscle spasm, and stiff neck.
• Cases transmitted via the faecal-oral route
• Polio was found everywhere 50 years ago, with 1% of those infected suffering from permanent paralysis.
• Effective vaccines are available making eradication possible.
• Polio mainly affects children <5yrs
• Polio cannot be cured, only prevented.
• In 1994, the WHO certified the Americas (36 countries) as polio-free, followed by the WHO Western Pacific Region (37 countries including China) in 2000 and the WHO European Region (51 countries) in June 2002
• In 2012, only three countries (Afghanistan, Nigeria, and Pakistan) remain polio-endemic.

Other Picornaviruses

• Rhinoviruses cause the common cold.
• Coxsackie causes throat infection, meningitis, plus hand, foot, and mouth disease.
• Hepatitis A is a liver infection spread faecally from an infected person.

Hepatitis Virus

• Hepatitis B is contracted through contact with infected body fluids, such as semen, blood, and saliva.
• The outcome of infection varies: about 1/3 develops a flu-like illness, and 1/3 develops full-blown hepatitis with high fever, abdominal pain, vomiting, and jaundice.
• Less than 1% of infections causes severe hepatitis
• Chronic carriers of hepatitis B are at risk for chronic liver problems (cirrhosis, liver cancer) and can spread the infection to others.
• Approximately 5% of the world's population are chronic carriers of HBV.
• Hepatitis C was identified in 1989.
• Approximately 0.5-1.0% of the UK population has chronic hepatitis C.
• Hepatitis C transmission is similar to HBV.
• Hepatitis C is often asymptomatic upon onset, and goes unnoticed for many years.
• HCV accounts for 20% of acute hepatitis, 70% of chronic hepatitis, 40% of end-stage cirrhosis, 60% of hepatocellular carcinoma, and 30% of liver transplants in industrialised countries.
• No vaccine with completely effective treatment is available.

Other Viruses

• Influenza is caused by influenza viruses.
• Measles is caused by the measles virus.
• Mumps is a viral illness caused by a paramyxovirus.
• Rubella is caused by the measles virus.
• Rabies is caused by the rabies lyssavirus.

Prions

• Prion diseases are caused by abnormally folded proteins (PrP) in the brain, leading to a progressive decline in brain function and are always fatal..
• Misfolded PrP accumulates and forms clumps that damage and kill nerve cells, causing tiny holes to form in brain tissue, making it appear sponge-like under a microscope.
• Prion diseases include Kuru (ritualistic cannibalism), sCJD (spontaneous conversion), f/gCJD (mutations in PRNP), GSS (mutations in PRNP), iCJD (infection with human prions), FFI (PRNP haplotype), vCJD (infection with BSE prions), and sFI (spontaneous conversion).