Chen J, Dang Q, Unutmaz D, Coffin JM, Pathak VK, Powell D, KewalRamani VN, Maldarelli F, Hu WS; HIV DRP Symposium Antiviral Drug Resistance (4th: 2003: Chantilly, Va.).
Program Abstr HIV DRP Symp Antivir Drug Resist. 2003 Dec 7-10; 4: Abstract no. 6.
HIV Drug Resistance Program, National Cancer Institute, NCI-Frederick, Frederick, MD 21702
Cells infected with two retroviruses can generate heterozygotic virions, which are the precursors of recombinant proviruses. Although many studies have focused on the frequencies and mechanisms of retroviral recombination, little is known about the dynamics of double infection. In this study, we examined the nature of HIV-1 double infection. Viruses were generated from two HIV-1 vectors containing different markers, mixed together, and used to infect target cells. The numbers of cells expressing none, one, or both markers were measured and used to calculate whether double infection occurred at frequencies expected from random infection events. We found that double infection occurred significantly more frequently than it would at random; this increased double infection was observed in both a T cell line and primary activated CD4+ T cells. In addition to direct virus infection, we also examined the nature of cell-mediated HIV-1 double infection. Increased double infection was observed in all experiments regardless of whether a cell line or primary human dendritic cells were used to capture and transmit HIV-1. We propose two mechanisms to explain the cause of the increased double infection. It is possible that HIV-1 infection is cooperative; infection of the first virus enhances the infection of the second virus. It is also possible that the population of target cells varies in their susceptibility to HIV-1 infection; double infection is enhanced in those cells that are more susceptible to infection, which leads to an overall increased double infection. These two mechanisms can be distinguished by viral infection kinetics. Our data are consistent with the hypothesis that target cell variation in susceptibility to virus infection causes the increased double infection. In summary, our results indicate that HIV-1 double infection occurs more frequently than it would at random in both direct and cell-mediated HIV-1 infections. This is the first direct evidence of nonrandom double infection in retroviruses. Frequent double HIV-1 infections in infected individuals would allow the generation of recombinant viruses that could then affect the pathogenesis of the virus and the evolution of HIV-1. Q.D. and J.C. contributed equally to this work.
Publication Types:
Keywords:
- Antigens, CD4
- Cell Line
- Communicable Diseases
- Dendritic Cells
- HIV Infections
- HIV-1
- Humans
- Retroviridae
- Retroviridae Infections
- T-Lymphocytes
- immunology
Other ID:
UI: 102268431
From Meeting Abstracts