Project: Research project

Project Details


Malaria is a growing public health problem. The transmission of malaria
parasites by vector species of Anopheles mosquitoes is difficult to
interrupt. The site-specific transmission potential of each vector
species is governed by the immediate environment, vector behavior, and
innate vector competence. The complex relationships which affect malaria
parasite transmission by Anopheles vectors are poorly understood and this
presents a major obstacle for effective malaria control. This proposal
seeks to investigate how species of Anopheles mosquitoes differ in their
ability to support the sporogonic development of Plasmodium parasites.
New approaches for examining innate vector competence and Plasmodium
development will provide insights into how basic mosquito-parasite
interactions affect patterns of transmission in nature.

Species of Anopheles mosquitoes from three major geographic areas of
malaria endemicity will be infected with in vitro cultured gametocytes
of P. falciparun, the most pathogenic human malaria. Parameters of
parasite development for each anopheline species, determined by
quantifying each major sporogenic stage over 20 d, will be related to
infections in a reference species included in each experiment. Profiles
of blood-feeding behavior and digestive physiology will be developed for
each anopheline species. These studies will define Anopheles species
differences in susceptibility and parasite development. Further
comparative studies on anopheline vector competence will focus on
environmental determinants of Plasmodium development, sporozoite invasion
and survival in the salivary glands, and sporozoite transmission. These
approaches for determining factors regulating the ability of Anopheles
mosquitoes to serve as malaria vectors will yield new information for
investigating malaria parasite transmission in nature, and for developing
and evaluating malaria control measure.
A number of biochemical features of the AIDS virus hamper efforts to
control the disease or prevent the spread of infection. Included among
them is the high degree of viral genetic variation, and therefore
antigenic variation, within the envelope protein. A multifaceted study
is proposed to correlate findings from a careful clinical and
immunological analysis of HIV1 in an infected male homosexual (referred
to as subject MA or 145) and an in-depth analysis of the diversity and
functional consequences of this diversity in viral envelope genes. Virus
isolates and cytotoxic T-lymphocyte (CTL) cell lines derived from
cerebrospinal fluid (CSF) and PBL will be generated and PBMC, serum and
semen samples will be obtained at frequent intervals. These will be
combined with an extensive list of materials and information already
available from this subject, including CTL lines, virus isolates. CSF
and other tissue samples and DNA sequence information, including samples
which bracket the onset of AZT therapy. Complete envelope genes will be
subjected to PCR amplification and cloning into a vaccinia virus
expression vector. PCR products will be subjected to heteroduplex,
restriction fragment length polymorphism and DNA sequence analyses over
the 3'700 bp of the gp120 coding sequence. Whole envelope proteins will
be expressed in vaccinia virus and evaluated for CTL recognition and
neutralization susceptibility, and inserted into a provirus backbone for
analysis of virus cell tropism, syncytium inducing capacity, and
cytopathogenicity. Extensive computer-aided analyses will be performed
to track viral genotypes and identify genetic features which correlate
with structural and functional differences. Detailed analysis of this
and subsequent subjects provides a unique opportunity to study the
natural history of infection and disease progression as well as provide
valuable insight into the response to antiviral therapy and potentially
vaccine design.
Effective start/end date1/1/9111/30/98


  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases


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