T U T O R I A L


Cesar D. Fermin, Ph.D. Tulane Pathology (504) 584-2521, Fax 504 587-7389

HUT-78 (H9) Cells + SF33 HIV

HIV particles attach to lymphocytes and penetrate after a short time. Infection follows with pathological transformation of the cells that lead to their death. Dr. Garry (Garry Lab home page) and Dr. Fermin published some of the transformations, and more details are found in (Publication) list.

Macroscopic transformations

Some of the changes induced by the contact of HIV with cell membranes and by penetration of the virus into the cell, are severe enough to be seen under the light microscope. Among others:

  • Condensation of the chromatin with significance for inducing apoptosis,

  • Fussion of cells to form giant cyncitia,

  • Complete rupture of the cells with release of infected content.

Immature HIV particle

These are characterized by a disorganized central core but otherwise a complete virus able to infect the lymphocytes. This particle is tightly attached to the membrane of this cell. We believe that membrane transformation caused by direct attachment is significant to the progression of AIDS.

Mature HIV particle

Attachment and penetration of the particles is not restricted to their maturation. Here a mature particle is attached to a portion of the membrane whose integrity was disrupted. The bilayer can be seen at a split point that could mark the site for membrane opening.

Membrane transformation by attachment and penetration

The area of the membrane near the particles is greatly modified. The arrowheads outline densities near the membrane that could correspond to just penetrated or exiting particles. Also note different stage of maturing particles outside.

Fusion of Infected cells

HIV infected cells fuse with touch each other and fuse. The cell on top (without nucleus) is fusing at this point with the cell on the bottom (with nucleus). The exact mechanism of fusion is unknown.

Multinucleated giant cells

These result from the fusion of many infected cells. The contact of the HIV particle with the membrane may initiate the fusion.

Budding from the Membrane

.Membrane densities like this are taken as indication that HIV particles are ready to exit the infected cell. The mechanism is well stablished and similar for virus type C like HIV. Note the perichromatin and the nuclear pores needed to get molecules in/out of the nucleus.

Acute infection

When cells are exposed to large numbers of virus, many particles are seen/micrometer square attached the cell membrane. When the particles beging to penetrate is not well understood.

Selective Attachment

Attachment of a single particle in the presence of other at the same level on the cell membrane points to selective aggregation of receptors on the membrane needed by the virus to attach. Even thought these three particles are equally proximal to the same area of the membrane only one is attached.