Analysis of ENV V3 sequences from HIV‐1‐infected brain indicates restrained virus expression throughout the disease

Abstract

The isolation of human immunodeficiency virus type 1 (HIV-1) from the cerebrospinal fluid (CSF) of asymptomatic virus carriers suggests that the viral infection spreading to the brain occurs early during infection. The aim of the present study was to investigate whether HIV-1 infection of the brain parenchyma also occurs during the early phase of infection. We also wished to compare the degree of replication of the virus in the brain at different clinical stages associated with HIV-1 infection. With the use of polymerase chain reaction (PCR), the viral genomes present in seven of eight brain specimens obtained from two asymptomatic HIV-1 carriers and six AIDS patients were amplified. Thereafter, the number of viral copies present in each brain specimen was quantified, the third variable region (V3) of the gp 120 glycoprotein was sequenced and these results compared with the histopathological findings in the tissue. The HIV-1 DNA genome was amplified from seven of the eight brain tissues, including the specimens obtained from the two asymptomatic carriers. An increased number of viral copies in the brain was found in association with histopathological findings of HIV-1 encephalitis. The analysis of the V3 sequences, however, revealed the presence of a homogeneous virus population in the brain at every clinical stage of the disease. These results suggest that, although entry of the virus in the parenchyma may occur early during infection, HIV-1 replication in the brain is constrained until the terminal phase of AIDS encephalitis.

Simian Immunodeficiency Virus Replicates to High Levels in Naturally Infected African Green Monkeys without Inducing Immunologic or Neurologic Disease

“…In infected humans, similar plasma HIV RNA levels are usually associated with rapid progression to AIDS (66). A recent report describing experimental infection of AGMs has demonstrated high-level plasma viremia and substantial replication in LN cells and PBMC at early times after experimental infection with a decline thereafter (25). In the present study, we demonstrated high levels of plasma viremia for naturally infected animals that had been infected for more than 10 years.…”

Intrathecal HIV-1 Envelope Glycoprotein gp120 Induces Enhanced Pain States Mediated by Spinal Cord Proinflammatory Cytokines

“…) invade the spinal cord. Using HIV-1 as the example, many HIV-1 variants are neurotropic (homing to the CNS) (Tyor et al, 1992) and concentrate in dorsal spinal cord (DiStefano et al, 1996). Because antiretroviral drugs used to treat HIV-1 do not cross the blood-brain barrier (VanLeeuwen et al, 1996), dorsal spinal cord infection would be expected to be unabated by current acquired immunodeficiency syndrome (AIDS) therapies.…”

Alteration of blood-brain barrier function by methamphetamine and cocaine

“…Among these agents is the HIV. The CNS is an early primary target of HIV invasion, because the virus and infected immunocytes appear early during the infection (Di Stefano et al 1996). The infection of the brain endothelium or choroid plexus by HIV-1 has been suggested (Moses et al 1993;Falangola et al 1995) and demonstrated for simian immunodeficiency virus (Edinger et al 1997).…”