Scientists have uncovered new evidence that strengthens the link between a host-cell gene called Apobec3 and the production of neutralizing antibodies to retroviruses. Published in the Sept. 5 issue of Science, the finding adds a new dimension to the set of possible explanations for why most people who are infected with HIV do not make neutralizing antibodies that effectively fight the virus. Antibodies are key to warding off viral infections, and most vaccines against viral diseases stimulate the body to make antibodies against the target virus. Yet no one knows how to make a vaccine that artificially stimulates the production of antibodies that can readily neutralize HIV, largely because so few HIV-infected people naturally exhibit this immune activity. The new finding about Apobec3 suggests that this gene may influence anti-HIV antibody production and may help explain why some people who are repeatedly exposed to the virus never become infected.

Researchers have discovered a new 'trick' that allows HIV to overtake resting T cells that are normally highly resistant to HIV infection, according to a report in the September 5th issue of the journal Cell, a Cell Press publication. The binding of the virus to the surface of those cells sends a signal that breaks down the cells' internal skeleton, a structure that otherwise may present a significant barrier to infection. Specifically, they show, binding of HIV to the receptor known as CXCR4 activates cofilin, a protein that disassembles actin microfilaments in the resting T cells. Those actin microfilaments are important building blocks of the cytoskeleton. That process is a required step for the virus to infect those resting cells, suggesting it may provide a useful new target for therapy, the researchers said. " The ability of co-receptor engagement to alter intracellular biochemistry suggests that exposure of cells to HIV may in fact prime cells for HIV infection," said Yuntao Wu of George Mason University and Jon Marsh of the National Institute of Mental Health. This first identification of the necessity of receptor signaling for infection also suggests "that HIV's evolved selection of co-receptors is borne out of necessity." In fact, the disassembly of actin microfilaments might actively assist HIV's entry into the nucleus, Wu added. "When actin is cut, it grows back. That process may carry the virus from the cortical actin to inside the nucleus."

Last year, researchers published headline-grabbing results from a series of clinical trials that found circumcised men in sub-Saharan Africa were 60% less likely to contract HIV than their uncircumcised counterparts over the course of two years (Lancet 369, 643–656; 2007; Lancet 369, 657–666; 2007). The mounting evidence transformed circumcision into a promising weapon in the meager HIV prevention arsenal. But, despite the strong data, efforts to roll out mass circumcision have met with continued resistance. In July, news agencies reported that elders from the Luo tribe, the third largest ethnic group in Kenya, had decided not to support circumcision as an HIV prevention strategy.

Recovery from Friend virus 3 (Rfv3) is a single autosomal gene encoding a resistance trait that influences retroviral neutralizing antibody responses and viremia. Despite extensive research for 30 years, the molecular identity of Rfv3 has remained elusive. Here, we demonstrate that Rfv3 is encoded by Apobec3. Apobec3 maps to the same chromosome region as Rfv3 and has broad inhibitory activity against retroviruses, including HIV. Not only did genetic inactivation of Apobec3 convert Rfv3-resistant mice to a susceptible phenotype, but Apobec3 was also found to be naturally disabled by aberrant messenger RNA splicing in Rfv3-susceptible strains. The link between Apobec3 and neutralizing antibody responses highlights an Apobec3-dependent mechanism of host protection that might extend to HIV and other human retroviral infections.

The virus that causes AIDS infects one form of immune T-cell by rearranging its inner skeleton, allowing it access to the cell, scientists have discovered. The finding helps explain how HIV maintains pockets of dormant virus in these so-called "resting" T-cells, even when the virus is under attack by antiretroviral drugs. It also points to potential new targets for drug development, experts say.

The spread of the Roman Empire through Europe could help explain why those living in its former colonies are more vulnerable to HIV. The claim, by French researchers, is that people once ruled by Rome are less likely to have a gene variant which protects against HIV. This includes England, France, Greece and Spain, New Scientist reports. Others argue the difference is linked to a far larger event, such as the spread of bubonic plague or smallpox.

Binding of the HIV envelope to the chemokine coreceptors triggers membrane fusion and signal transduction. The fusion process has been well characterized, yet the role of coreceptor signaling remains elusive. Here, we describe a critical function of the chemokine coreceptor signaling in facilitating HIV infection of resting CD4 T cells. We find that static cortical actin in resting T cells represents a restriction and that HIV utilizes the Gαi-dependent signaling from the chemokine coreceptor CXCR4 to activate a cellular actin-depolymerizing factor, cofilin, to overcome this restriction. HIV envelope-mediated cofilin activation and actin dynamics are important for a postentry process that leads to viral nuclear localization. Inhibition of HIV-mediated actin rearrangement markedly diminishes viral latent infection of resting T cells. Conversely, induction of active cofilin greatly facilitates it. These findings shed light on viral exploitation of cellular machinery in resting T cells, where chemokine receptor signaling becomes obligatory.

Scientists have uncovered new evidence that strengthens the link between a host-cell gene called Apobec3 and the production of neutralizing antibodies to retroviruses. Published in the Sept. 5 issue of Science, the finding adds a new dimension to the set of possible explanations for why most people who are infected with HIV do not make neutralizing antibodies that effectively fight the virus. Antibodies are key to warding off viral infections, and most vaccines against viral diseases stimulate the body to make antibodies against the target virus. Yet no one knows how to make a vaccine that artificially stimulates the production of antibodies that can readily neutralize HIV, largely because so few HIV-infected people naturally exhibit this immune activity. The new finding about Apobec3 suggests that this gene may influence anti-HIV antibody production and may help explain why some people who are repeatedly exposed to the virus never become infected. HIV is a retrovirus, a type of virus that incorporates its genetic material into the DNA of its host cell. Retroviruses infect many mammals, and mice are susceptible to a retrovirus called Friend virus. A single gene controls the ability of mice to make neutralizing antibodies against this retrovirus and to recover from the viral infection. New research sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, demonstrates that this single, powerful gene is Apobec3, a gene found in matching locations in mice and humans. The scientists who conducted the study hypothesize that Apobec3 in humans might play a similar role in helping shape the neutralizing antibody response to human retroviruses such as HIV. Their thinking is supported by previous studies showing that human Apobec3 proteins exert anti-HIV activity and that the human chromosomal region containing Apobec3 genes influences the ability of the virus to establish infection.

The AIDS virus is especially hard to fight because few people develop antibodies to neutralize it, but U.S. researchers said on Thursday they have found an immunity gene that may offer a new way to fight back. They said the gene Apobec3 helps mice develop antibodies against an HIV-like virus, and they think the same gene in humans could lead to a potent vaccine against the human immunodeficiency virus or HIV.