Virology: Virus Replication and Viral Illnesses

General Principles of Virology

• Viruses require a host cell for replication
• Viruses attach to a host cell, enter it, and use the host's resources, such as energy, DNA, and RNA to replicate
• Viruses are small and harder to kill, since they live inside cells.
• Antiviral drugs can harm the host cell

Virus Replication

• Viruses attach to a host cell
• The virus is uncoated and enters the host cell nucleus
• Viral DNA and RNA are controlled, with protein production
• Viral subunits are made
• Virions assemble
• Virions are released

Viral Illnesses

• Common viral illnesses include Smallpox (poxviruses), sore throat and conjunctivitis (adenoviruses), and warts (papovaviruses)
• Influenza (orthomyxoviruses) and respiratory infections (coronaviruses, rhinoviruses) are viral illnesses
• Viral gastroenteritis (rotaviruses, norwalk-like viruses), HIV/AIDS (retroviruses), herpes (herpesviruses), and hepatitis (hepadnaviruses) are viral illnesses
• Most viral illnesses are survivable
• Effective vaccines prevent some illnesses
• Effective drug therapy is available for few infections

Antiviral Drugs

• Antiviral drugs suppress viruses by destroying virions or preventing replication and are controlled by antiviral therapy
• Immunoglobulins are antibodies that attack and destroy viruses
• Viruses controlled by current antiviral therapy include Cytomegalovirus (CMV), Hepatitis viruses, and Herpesviruses
• Other viruses controlled include HIV, Influenza viruses (“flu”), and Respiratory syncytial virus (RSV)

Antiviral Drug Characteristics

• Antiviral drugs able to enter infected cells interfere with viral nucleic acid synthesis/regulation, and prevent fusion.
• Some antivirals stimulate the body’s immune system
• Those with competent immune systems respond best to antiviral medication
• A healthy immune system and drug work synergistically to eliminate/suppress viral activity

Focus of Antiviral Drugs

• Opportunistic infections occur in immunocompromised patients and require long-term treatment.
• Opportunistic infections can be viruses, fungi, bacteria, or protozoa
• Antiviral drugs treat infections from viruses that are not HIV
• Antiretroviral drugs treat infections caused by HIV which causes AIDS

Herpes Simplex and Varicella-Zoster Virus Infections

• Herpesviridae includes herpes simplex virus (HSV) 1 (oral herpes) and HSV 2 (genital herpes)
• Herpesviridae includes Human herpesvirus (HHV 3), also known as varicella-zoster virus (VZV) (chickenpox and shingles )
• Herpesviridae includes HHV 4: Epstein-Barr virus and HHV 5: CMV
• Herpesviridae includes HHV 6 and HHV 7, that are not clinically significant; immunocompromised patients AND HHV 8 (Kaposi's sarcoma)
• HSV 2 (genital herpes) is highly transmissible and can cause "Neonatal” herpes
• HHV 3 (VZV) causes chickenpox, and there is a varicella virus vaccine
• HHV 3 (VZV) also causes shingles, for which opioids may be needed for pain control
• Postherpetic neuralgias are a symptom of HHV 3 (VZV)
• Acyclovir may speed recovery; best results are generally seen when antiviral medication is started within 72 hours of symptom onset
• Zostavax® is a treatment for this virus

Hepatitis C

• The leading cause of chronic liver disease and a common reason for liver transplantation
• ribavirin (Virazole®) can be taken orally for treatment

Mechanism of Action for Non-HIV Antiviral Drugs

• They inhibit activity of polymerase enzyme that stimulates new viral genome synthesis

Non-HIV Antiviral Use

• Used to treat influenza viruses, HSV, VZV, CMV, and Hepatitis A, B, and C

Non-HIV Antiviral Drugs: Adverse Effects & Interactions

• Adverse effects of non-HIV antiviral drugs vary with each drug
• Healthy cells are often killed causing toxicities
• Drug Interactions

Non-HIV Antiviral Drug: amantadine hydrochloride (Dom-Amantidine®)

• Narrow antiviral spectrum, active only against influenza A
• Recent guidelines deter use for influenza treatment or prevention
• Causes central nervous system and gastrointestinal effects

Non-HIV Antiviral Drug: acyclovir (Zovirax®)

• A synthetic nucleoside analogue, is used to suppress replication of HSV 1, HSV 2, and VZV
• Is the medication of choice for initial and recurrent episodes
• Comes in oral, topical, and parenteral forms

Non-HIV Antiviral Drug: ganciclovir hydrochloride (Cytovene®, Valcyte®)

• A synthetic nucleoside analogue of guanosine, to treat CMV infections
• Available in oral and parenteral forms
• Used to treat CMV retinitis

Similar Non-HIV Antiviral Drugs

• Valacyclovir hydrochloride, and famciclovir, are oral forms and treat less severe infections

Non-HIV Antiviral Drugs: Neuraminidase Inhibitors

• Oseltamivir phosphate (Tamiflu) and zanamivir (Relenza) treat influenza A and B, and reduce duration
• Oseltamivir phosphate is an oral drug that causes nausea and vomiting
• Zanamivir is an inhaled drug, causes diarrhea, nausea, and sinusitis
• Treatment should begin within 2 days of influenza symptoms

Non-HIV Antiviral Drug: Ribavirin

• A synthetic nucleoside analogue, administered through oral, nasal inhalation or inhalation
• Inhalation form (Virazole) is used for hospitalized infants with respiratory syncytial virus

HIV and AIDS

• 36.9 million people worldwide are infected with HIV
• HIV is a retrovirus, transmitted by sexual activity, intravenous drug use, and perinatal transfer
• Risk for transmission to health care workers via needle-stick injuries is approximately 0.3%
• Hand hygiene and precautions are extremely important

Stages of HIV Infection

• Stage 1: Asymptomatic infection
• Stage 2: Early, general symptoms of disease
• Stage 3: Moderate symptoms
• Stage 4: AIDS-defining illnesses, often leading to death

Opportunistic Infections

• Infections caused by organisms that an immunocompetent person would normally not get
• Common in those with cancer, organ transplant recipients, and individuals who have AIDS
• Caused by non-HIV viruses, bacteria, fungi, and protozoans
• Require long-term prophylactic anti-infective drug therapy

Antiretroviral Drugs

• Highly active antiretroviral therapy, includes at least three medications, reduce the viral load

Antiretroviral Drug Classes

• Reverse transcriptase inhibitors block activity of reverse transcriptase, to prevent production of new viral DNA
• Protease inhibitors inhibit protease retroviral enzyme to prevent viral replication
• Fusion inhibitors inhibit viral fusion to prevent viral replication
• Entry inhibitors: CCR5 co-receptor antagonists
• Integrase inhibitors are also used

Antiretroviral Drugs: Adverse Effects

• Numerous and vary with each medication
• Drug therapy may need to be modified due to adverse effects
• Goal is to find best regimen to control infection, with tolerable effect profile
• Medication regimens change during course of illness

Antiretroviral Drug: enfuvirtide (Fuzeon®)

• A fusion inhibitor and suppresses the fusion process, preventing virion attachment to T cells
• Treats HIV infection with other antiretrovirals and reduces viral loads
• It is available only in injectable form

Other Viral Infections

• Other viral infections include: Avian influenza (“bird flu”), West Nile virus, Severe acute respiratory syndrome (SARS), and H1N1 influenza virus (“swine flu”)

Nursing Implications for Antiviral Therapy

• Assess for underlying disease, medical history, and allergies
• Assess baseline VS and nutritional status and assess for contraindications, cautious use conditions, potential drug interactions
• Teach proper technique for applying ointments/powders and emphasize handwashing
• Instruct patients to wear gloves with ointments/solutions to affected areas
• Instruct patients to consult prescribers before taking other medications
• Emphasize good hygiene and inform patients that drugs manage symptoms
• Instruct patients on importance of taking prescribed medications, complete the course of prescribed treatment, and start therapy early
• Monitor for adverse and therapeutic effects

Case Studies

• Acyclovir suppresses the replication of HSV-1, HSV-2, and varicella-zoster virus

• Zanamivir treats active influenza

• Ribavirin treats neonates with RSV

• Indinavir must be taken with at least 1.5 L of fluids daily

Immunity

• Antigens are foreign proteins from invading organism imprinted into memory, to fight it effectively next invasion
• Antibodies are immunoglobulin molecules with antigen-specific amino acid sequences, synthesized

Active Immunization

• Artificial active immunization is clinical exposure harmless antigen that doesn’t cause infection
• Natural active immunization acquires immunity by surviving and producing antibodies against the organism

Artificial Active Immunization

• The body is exposed to a relatively harmless form of an antigen, and the immune system is stimulated, and “remembers” the antigen
• The antigen does not cause infection

Natural Active Immunization

• Immunity through survival, producing antibodies

Passive Immunity

• Artificial passive: administration of serum or concentrated immunoglobulins. Bypasses hosts system
• Natural passive: antibodies transferred from mother to infant in breast milk or via the placenta

Biological Antimicrobial Drugs

• Used to prevent/treat/cure infections and are called biologicals
• Biological Antimicrobial Drugs examples: Antitoxins, antisera, and toxoids / vaccines, which target a infectious microorganism

Toxoids

• Antigenic preparations of bacterial exotoxins
• Detoxified with chemicals or heat, weakened/attenuated and cannot revert back to a toxic form
• Stimulate the immune system to produce a specific antibody, an artificial active immune response
• Protect against future exposures (e.g., diphtheria, tetanus)

Vaccines

• Suspensions of live, attenuated (weakened) or killed (inactivated) microorganisms prevent disease
• Stimulate antigens to produce antibodies, also. Live vaccines are lifelong, killed are partial
• Example: Influenza and pneumonia vaccines

Inactivated Drugs

• Hepatitis B virus vaccine (inactivated) (Recombivax HB®, Engerix-B®): Noninfectious viral vaccine containing hepatitis B surface antigen (HBsAg).
• Antigenic HBsAg promotes active immunity for those at high risk and is for children and adult diabetics

Influenza Vaccine

• A vaccine has to be given each year before influenza season
• FluMist Quadrivalent is given intranasally, others are given intramuscularly/intradermally
• The National Advisory Committee on Immunization recommends all are vaccinated after 6 months old
• Fluad for adults over 65

Other Vaccines

• Live vaccines: measles, mumps, and rubella virus vaccine
• Other inactivated vaccines: Meningococcal, pneumococcal, polyvalent, and 13 valent, Poliovirus, Rabies virus, Human papillomavirus, Herpes zoster, Varicella virus