MICROBIO 2.7 - ENVELOPED RNA RETROVIRUSES

• Retroviruses are enveloped RNA viruses.

Module Review

• The module includes Lentivirus (HIV), Hepatitis Virus, and CBL virus as well as the basics of bacteria.

HIV Statistics (2019)

• People living with HIV: 38.0 million
• Newly infected with HIV: 1.7 million
• HIV-related deaths: 690,000
• HIV was first identified in 1981

Class Objectives

• Key objectives include:
  • Differentiating between naked and enveloped RNA viruses
  • Describing HIV among enveloped RNA viruses
  • Listing components of the HIV virion
  • Describing HIV pathogenesis
  • Diagnosing enveloped RNA viruses
  • Prescribing prevention and treatments
  • Understanding reverse transcriptase and integrase inhibitors

Retroviruses Key Concepts

• Pathogens: Retroviruses are RNA viruses with reverse transcriptase, allowing them to use RNA to make DNA.
• Examples of retroviruses include Human Immunodeficiency Virus (HIV), human T-cell Leukemia virus type I (HTLV -I) and HTLV-II
• Encounter: HIV is now a worldwide ongoing pandemic from the early 1980's.
• Entry: HIV can be transmitted through sexual contact, injection drug use, and vertically (mother to child).
• Spread: HIV binds to the CD4 molecule, enters helper T cells and monocytes, and infects these cells.
• Replication: Retroviruses may cause disease years after initial infection; HIV has a long latency period of ten years.
• Damage: HIV infection of CD4+ T lymphocytes disables the immune system and makes the infected vulnerable to opportunistic infections; HIV displays antigenic variation.
• Diagnosis: Screening is done by testing for HIV and other retrovirus antibodies. Confirmation and quantification of infection can be done using nucleic acid amplification techniques.
• Treatment: Antiviral drug treatment of HIV is highly effective.
• Prevention: Vaccine development has been slow, but recent advances in microbicides and antiretroviral drugs as preventative agents can reduce HIV transmission spread.

Retrovirus Structure

• Envelope glycoproteins (VAPs) help mediate fusion between virion & cell
  • gp120 finds cells then binds to co-receptors (CCR5 or CXCR4)
  • gp41 helps with cellular fusion
• M protein links viral envelope with virus core.
  • gag is a group-specific antigen and a major structural protein
• Antigens
  • p24 antigen- makes up the capsid for detection of infection.
• Reverse transcriptase (RT) converts RNA to DNA so it can enter the nucleus to combine with host genetic material.

Pathogenesis of HIV-I Infection

• HIV infects CD4+ T cells, monocytes, and macrophages
• Majority of replication occurs in productively infected CD4+ lymphocytes.

Retrovirus Replication Cycle

• Recognition & Attachment: gp120 binds to CD4+ then CCR5 or CXCR4 binds as a co-receptor.
• Penetration: gp41 fuses with the viralmembrane and the cell membrane.
• Macromolecular Synthesis: DNA is synthesized via reverse transcriptase from RNA.
• Integration: DNA molecule is transported to the nucleus and is integrated into the host cell chromosome using integrase.
• Synthesis of progeny virus: in the eclipse phase (aka productive infection), DNA is transcribed to mRNA, and mRNA translated to proteins. During the latent period, cells contain the virus without active replication or viral RNA/protein expression.
• Assembly & Budding

HIV Transmission & Prevention

• HIV can be transmitted through sexual contact, from mother to baby through Transfusions, or by sharing injecting equipment
• HIV cannot be transmitted through kissing, hugging, sharing food, insect bites, toilet seats, bathing, or sneezes and coughs.
• Safe sex (condoms) and the use of new needles can help prevent transmission.

Symptoms of HIV Infection

• The main symptoms of an acute infection are fever and weight loss
• Weight loss, a sore throat or mouth, and muscle pain are indicative of an acute infection
• Symptoms of AIDS include Encephalitis, Meningitis, Pneumonia, Tuberculosis and Tumors

CD4 T Cells vs. Monocytes/Macrophages

• Monocyte turnover (Macrophage) refers to the rate at which macrophages, a type of immune cell, are replaced in the body.
• CD4 T Cells are targeted by the HIV virus

HIV-Associated Neurocognitive Disorders (HAND) Classification

• Asymptomatic neurocognitive impairment (ANI) is the mildest form.
  • Occurs in 30% of CART-treated HIV-positive individuals, with impairment in at least two cognitive domains.
• Mild neurocognitive disorder (MND): Affects 20–30% with mild to moderate interference in daily functioning.
• HIV-associated dementia (HAD) is the most severe form.
  • Affects 2–8% with marked impairment in at least two cognitive domains leading to substantial interference in daily functioning.

HIV Treatment & Prevention

• Prevention includes practicing safe sex by using condoms and using new needles.
• Treatment includes the used of antibody receptor antagonists or peptide antagonists. These include Heparan sulfate and dextran.
• Penetration & Uncoating: Fusion inhibitors can block the process.
• Also use inhibitors, genome replication, HIV reverse transcriptase, and Viral integrase.

Combination Anti-Retroviral Therapy (CART)

• More-effective therapies in CART have reduced the severity of HIV-related cognitive disorders

Explore HIV medication mechanisms, focusing on Enfuvirtide's action on the viral replication cycle. Learn about antiretroviral drug classes, like integrase inhibitors, and their impact on viral DNA integration. Understand the role of protease inhibitors and glycoprotein gp120 in HIV treatment.