HIV variability and host control in HIV pathogenesis.
Int Conf AIDS 1996 Jul 7-12; 11:15 (abstract no. We.A.500) Levy JA, Blackbourn DJ, Barker E, Mackewicz C, Stranford S; Cancer Research Institute and Dept. of Medicine, University of California, San Francisco, CA, USA. Fax: 415-476-8365. E-mail: jalevy@itsa.ucsf.edu.
HIV undergoes genetic mutations in the infected host leading to the emergence of a variant virus with properties associated with virulence. These include an expanded host cell range, rapid kinetics of virus replication with high levels of virus production, and increased killing of CD4+ lymphocytes. Asymptomatic individuals and those who are long-term survivors of HIV infection often demonstrate the presence of a noncytopathic viral strain in their blood. Host immune response is important in controlling virus replication in infected individuals. Antibodies produced in asymptomatic individuals can neutralize the autologous virus, while in progressors, enhancing antibodies can be detected. Most importantly, CD8+ cell responses in people who remain asymptomatic show the ability to suppress virus replication in HIV-infected CD4+ cells. This activity is observed with CD8+ cells from both peripheral blood and lymph nodes of infected individuals. A reduction in this response appears to occur first in lymphoid cells and can presage development of disease. The mechanism for this suppression of HIV replication involves, in part, a novel cellular factor which is unlike other previously characterized cytokines and chemokines. CD8+ CD28+ cells show high levels of this antiviral response and antibodies to CD28 can enhance the antiviral activity and production of CAF. Moreover, many subjects at high risk for HIV infection but uninfected show this CD8+ cell antiviral response which is not detected in normal uninfected individuals. Present studies are directed at demonstrating how CD8+ cells (and CAF) can protect against infection and provide long-term survival to infected individuals.
Keywords: AEGIS, HIV, HIV Infections, Virus Replication, CD4-Positive T-Lymphocytes, Antigens, CD8, HIV Core Protein p24, HIV Long-Term Survivors, HIV Long Terminal Repeat, HIV Seronegativity, Antigens, CD28, prevention & control, virology, genetics, immunology, ICA11
