Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages

Abstract

Autophagy is a cytoplasmic degradative pathway that can participate in biosynthetic processes, as in the yeast Cvt pathway, but is more commonly known for its functions in removing damaged or surplus organelles and macromolecular complexes. Here, we find that autophagy intersects with human immunodeficiency virus (HIV) biogenesis, mirroring the above dichotomy. Early, nondegradative stages of autophagy promoted HIV yields. HIV Gag-derived proteins colocalized and interacted with the autophagy factor LC3, and autophagy promoted productive Gag processing. Nevertheless, when autophagy progressed through maturation stages, HIV was degraded. This, however, does not occur, as the HIV protein Nef acts as an antiautophagic maturation factor through interactions with the autophagy regulatory factor Beclin 1, thus protecting HIV from degradation. The dual interaction of HIV with the autophagy pathway enhances viral yields by using the early stages while inhibiting the late stages of autophagy. The role of Nef in the latter process enhances yields of infectious HIV and may be of significance for progression to clinical AIDS.

Apoptotic-likeLeishmaniaexploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination

“…Autophagy plays a positive role in the replication of Brucella abortus and may assist in HIV biogenesis. 21,22 Moreover, induction of autophagy correlates with an increased Leishmania parasite load. 23 Focusing on the latter one, we could already show that the virulent Leishmania inoculum consists partially of apoptotic-like parasites, through which disease development can occur.…”

Increased formation of autophagosomes in ectromelia virus-infected primary culture of murine bone marrow-derived macrophages

“…Some viruses have evolved mechanisms to subvert autophagic machinery to facilitate replication in macrophages. It has been demonstrated that replication of human immunodeficiency virus 1 (HIV-1) was severely impaired in macrophages treated with the autophagy inhibitor 3-methyladenine (3-MA) and in Beclin 1 or Atg7 siRNA-transfected cells (Kyei et al, 2009). Moreover, pharmacological induction of autophagy by rapamycin enhanced yields of virus released from macrophages (Kyei et al, 2009).…”

“…It has been demonstrated that replication of human immunodeficiency virus 1 (HIV-1) was severely impaired in macrophages treated with the autophagy inhibitor 3-methyladenine (3-MA) and in Beclin 1 or Atg7 siRNA-transfected cells (Kyei et al, 2009). Moreover, pharmacological induction of autophagy by rapamycin enhanced yields of virus released from macrophages (Kyei et al, 2009). On the contrary, Campbell and Spector (2012) found that vitamin D could inhibit HIV-1 replication in macrophages through autophagy induction, and treatment of cells with bafilomycin A (BFA, an inhibitor of the lysosomal vacuolar-ATPase) and knockdown of Beclin 1 and Atg5 counteracted the inhibitory effect of vitamin D. Because autophagy is involved in many biological functions, the exact role of autophagy in ECTV infection should be clarified in future studies.…”

TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity

“…Fluorescence confocal microscopy was performed as described previously (Kyei et al, 2009). Images were acquired using a microscope (META; Carl Zeiss) equipped with a 63×/1.4 NA oil objective, camera (LSM META; Carl Zeiss), and AIM software (Carl Zeiss).…”

“…The reagents used were Ultrapure LPS (InvivoGen), IFN-γ (PeproTech), Cytotoxic LDH assay (Promega), and TO-PRO-3 Iodide (Life Technologies). Immunoblotting and immunostaining were conducted as previously described (Kyei et al, 2009). FAM-YVAD-FMK stainings (FLICA; ImmunoChemistry Technologies) were performed according to the manufacturer's instructions.…”