Retroviruses

RNA viruses that require host cells and host machinery for replication and propagation.

Human T-Lymphotropic Virus (HTLV)

Can be transmitted by sexual contact, breast feeding, blood transfusion, or bites from infected primates.

Both HTLV-1 and 2 can cause HTLV associated myelopathy (HAM) and tropical spastic paraparesis (TSP). Only HTLV-1 can cause acute T-cell leukemia/lymphoma.

Pathology

Cell proliferation: Activation of oncogenes fos and erb as well as IL-2
Chronic inflammation: Increase in IFN-gamma

Diagnosis

EIA (enzyme linked immunoassay) test which which utilizes antibody detection. This can be confirmed via western blot (antigen detection).

This isn't as useful for infants as they hold their mother's antibodies for a year or so. Therefore, PCR testing is a better solution for those cases.

Prevention

• Blood donation screening
• Avoid breastfeeding or limit to the first 6 months of life if mother is known to have HTLV infection
• Wrap that shit up boys

Treatments

Symptom management only.

HTLV-1 associated acute T-cell leukemia and lymphoma

Lab findings include peripheral blood cells with “flower cells”. Will also see high WBC.

• Generalized lymphadenopathy
• Hypercalcemia from dysregulation of parathyroid hormone (PTH)
• Lytic bone lesions from dysregulation of parathyroid hormone (PTH)
• Skin lesions: Papules, nodules, or microabscesses (mycosis fungoides from cutaneous infiltration of proliferating cells)

HTLV associated myelopathy (HAM) and tropical spastic paraparesis (TSP)

Autoimmunity via antigen mimicry as well as direct infection of microglial cells and astrocytes. Associated with blood transfusions.

Exam findings will include stiff gait, spasticity, weakness in extremities, positive Babinski sign, and clonus.

• Lower back and leg pain
• Urinary symptoms: Incontinence, impotence
• Paresthesia: Pins and needles feeling in extremities

Human Immunodeficiency Virus (HIV)

Transmitted via direct contact either through mucous membranes, needles, transfusions, or mother-to-child transmission.

Co-occurring STIs increase the risk of acquiring HIV via sexual contact as they can increase the number of immune cells in mucosal surfaces. This means more targets for HIV.

One of the ways HIV enters the host’s cells is via the CCR5 receptor. Because of this, individuals with defects in CCR5 function have a lower risk of contracting HIV.

Pathology

The main target of HIV viral particles is CD4 receptor containing cells.

1. HIV viral particles bind CD4 receptors on dendritic cells in the presence of chemokine receptor CCR5
2. Dendritic cells fuse with CD4 T-cells
3. Cells replicate

Viral particles are detectable within 2 days in the draining internal iliac lymph nodes. They cause destruction of CD4 T-cells as well as macrophage lineage cells. Inflammation from the infection can also destroy uninfected CD4 cells.

Diagnosis

Immunoassays (EIA) and western blots are no longer used as antibodies against HIV are formed slowly. Instead, an HIV RNA test is used which detects infection less than 1-2 weeks post-infection. An alternative is 4th generation IgM antibody testing plus p24 antigen detection which is highly sensitive and specific, but requires more time post-infection to return positive (over 2 weeks).

If a follow-up confirmation test is negative, a nucleic acid amplification assay should discriminate more properly.

Phase 1: Dissemination

Associated with positive HIV RNA but negative HIV antibody (no adaptive immune response yet). Viral load also increases rapidly but then decreases as the body starts to control viral replication. This phase is most contagious because of the increased viral load.

Around 40-90% of patients have symptoms. These can include flu-like symptoms like fever, adenopathy, pharyngitis, rash, myalgia (muscle pain), arthralgia (joint pain), headache, nausea, vomiting, night sweats, and weight loss.

Phase 2: Latent

Asymptomatic while the virus hibernates in T memory cells. Lasts around 10-years. Over this time, CD4 T-cells decline at a steady rate.

Phase 3: AIDS

Eventually, there is a sharp drop-off in CD4 T-cell count when they start losing to viral load and new infections. AIDS kicks in when CD4 T-cell count drops below 200 and more opportunistic infections begin.

Progression Types

Typical

After about 8-10 years, either the CD4+ T cells will reach a level below 200 or the individual will start to develop opportunistic infections.

Rapid

Will progress to AIDS within only a few years, which ultimately results in death

Long-term survivors

Maintain high CD4+ cell counts for up to 20 years. Eventually they will need therapy.

Long-term non-progressors

Medical miracles. They have undetectable viral loads for years and maintain elevated levels of CD4 cells persistently.