Question

What is correct about the "Trojan Horse" model of HIV invasion into the CNS? a. Proposes that monocyte-macrophage carry progeny virions from blood to the brain inside cytoplasmic vacuoles and across the blood-brain barrier b. Requires an inflammatory response in the brain, which elicits a chemokine gradient c. After infiltrating the brain parenchyma, blood borne monocyte-macrophages also release additional chemokines and further attract additional inflammatory cells d. Does not require productive viral replication in brain microvascular endothelial cells e. All of the above

Short answer

A. The model proposes that monocyte-macrophages carry progeny virions from the blood to the brain inside cytoplasmic vacuoles and across the blood-brain barrier. B. The Trojan Horse model requires an inflammatory response in the brain, eliciting a chemokine gradient. C. After infiltrating the brain parenchyma, blood-borne monocyte-macrophages also release additional chemokines and further attract additional inflammatory cells. D. The Trojan Horse model does not require productive viral replication in brain microvascular endothelial cells. E. All of the above. Answer: E. All of the above.

Step-by-step solution

Understand the Trojan Horse Model of HIV Invasion into the CNS

The Trojan Horse model describes how HIV enters the central nervous system (CNS) by using monocyte-macrophages as carriers, which cross the blood-brain barrier and deliver the virus into the CNS.

Evaluate Option A

Option A states that this model proposes monocyte-macrophages carry progeny virions from the blood to the brain inside cytoplasmic vacuoles and across the blood-brain barrier. This is in line with the Trojan Horse model, as it highlights the role of monocyte-macrophages in HIV invasion into the CNS.

Evaluate Option B

Option B states that the Trojan Horse model requires an inflammatory response in the brain, eliciting a chemokine gradient. This is also correct because the inflammatory response is necessary for monocyte-macrophages to be attracted to the site of infection and subsequently infiltrate the CNS.

Evaluate Option C

Option C says that after infiltrating the brain parenchyma, blood-borne monocyte-macrophages also release additional chemokines and further attract additional inflammatory cells. This is true, as it adds to the inflammatory reaction and allows the spread of the infection within the CNS.

Evaluate Option D

Option D claims that the Trojan Horse model does not require productive viral replication in brain microvascular endothelial cells. This is also correct, as the primary focus of the model is on the role of monocyte-macrophages carrying the virus, rather than viral replication within the CNS.

Choose the Correct Answer

Since all options A, B, C, and D are consistent with the Trojan Horse model of HIV invasion into the CNS, the correct answer is option E, which states that all of the above are correct.

Key concepts

HIV infiltration

The Trojan Horse model aims to explain how HIV breaches the central nervous system (CNS) defenses. Primarily, it suggests that HIV doesn't directly infiltrate the brain. Instead, it leverages a "Trojan Horse" approach using immune cells. These cells, specifically monocyte-macrophages, function as carriers. They transport HIV across the blood-brain barrier (BBB) without alerting the body's defenses.

• Monocyte-macrophages pick up HIV in the blood.
• They carry the virus within cytoplasmic vacuoles.
• Cross the BBB to deliver HIV into the brain.

This method allows HIV to enter and persist in the brain, potentially leading to severe complications down the line. Thus, understanding HIV infiltration is crucial for addressing CNS-related symptoms in HIV patients.

monocyte-macrophage

In the context of the Trojan Horse model, monocyte-macrophages play a pivotal role. They are part of the immune system and act as transporters for HIV, helping the virus to traverse physical barriers and immune defenses. Here's how they contribute to HIV invasion into the CNS:

• They are highly mobile, circulating in the bloodstream and migrating to areas where they're needed.
• Monocyte-macrophages can be hijacked by HIV, which uses them as vessels to cross into the brain.
• Inside these cells, the virus can remain hidden and shielded from immune detection.

Their role as a "Trojan Horse" highlights the deceptive strategy HIV employs. Understanding their function aids researchers in developing tactics to potentially intercept or block this transport before HIV reaches critical areas like the brain.

blood-brain barrier

The blood-brain barrier (BBB) is a vital protective mechanism that segregates the CNS from the rest of the body. Its primary role is to regulate what can and cannot enter the brain, ensuring harmful substances are kept out. Here’s what you should know:

• The BBB is composed of tightly packed endothelial cells, forming a selective barrier.
• While keeping pathogens and toxins out, it must also allow essential nutrients to pass through.
• Monocytes can pass through the BBB, but only under certain conditions, such as inflammation.

When HIV manipulates monocyte-macrophages to cross the BBB, it effectively breaches a major line of defense, leading to potential neurological complications. Understanding the function and permeability of the BBB is crucial in comprehending HIV’s deleterious effects on the CNS.

CNS inflammation

Once the immune cells carrying HIV infiltrate the CNS, inflammation often follows. This inflammatory response can exacerbate neurological damage and contribute to various symptoms in patients. Here's the sequence involved:

• Immune cells release chemokines upon entering the brain, which attract other inflammatory cells.
• This cascade amplifies the inflammatory response, potentially damaging brain tissues.
• Persistent inflammation might lead to cognitive impairments and other neurological issues.

Addressing CNS inflammation in HIV patients is significant because it can help mitigate the neurological symptoms associated with HIV infection. By targeting the inflammation, doctors hope to improve quality of life and limit disease progression.